Thirteen novel [1,2,4]triazolo[4,3-c]quinazoline derivatives as DNA intercalators were synthesize... more Thirteen novel [1,2,4]triazolo[4,3-c]quinazoline derivatives as DNA intercalators were synthesized and their anticancer activities evaluated against HepG2 and HCT-116 cells. A docking study was carried out to explore how the new derivatives bind to active sites of DNA. The docking data were highly interrelated with that of biological testing. The HCT-116 cell line was the most sensitive one to the effect of the new derivatives. Compound 7c exhibited the highest anticancer activities against both the HepG2 and HCT116 cancer cell lines. Despite this compound displaying less activity than doxorubicin, it could be useful as a template for future manipulation, optimization, and investigation to produce other analogs with potential activity. The most active derivatives, 7c , 7b , and 7a were evaluated as DNA binders. Compound 7c displayed the highest binding affinity. Furthermore, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) profile was calculated for the four most active compounds in comparison to doxorubicin as reference drug. Our derivatives 7a , 7b , and 7c displayed a very good calculated ADMET profile in comparison to doxorubicin.
Novel heterocyclic derivatives (4–22) were designed, synthesized, and evaluated against hepatocel... more Novel heterocyclic derivatives (4–22) were designed, synthesized, and evaluated against hepatocellular carcinoma type (HepG2) and breast cancer (MCF‐7) cells, targeting the VEGFR‐2 enzyme. Compounds 18, 10, 13, 11, and 14 were found to be the most potent derivatives against both the HepG2 and MCF‐7 cancer cell lines, with GI50 = 2.11, 2.54 µM, 3.16, 3.64 µM, 3.24, 6.99 µM, 7.41, 6.49 µM and 8.08, 10.46 µM, respectively. Compounds 18 and 10 showed higher activities against both HepG2 and MCF‐7 cells than sorafenib (GI50 = 9.18, 5.47 µM, respectively) and doxorubicin (GI50 = 7.94, 8.07 µM, respectively). Compounds 13, 11, and 14 showed higher activities than sorafenib against HepG2 cancer cells, but lower activities against MCF‐7 cells. Compounds 18, 13, and 10 were more potent than sorafenib, inhibiting vascular endothelial growth factor receptor‐2 (VEGFR‐2) at GI50 values of 0.05, 0.06, and 0.08 µM, respectively. Compound 11 inhibited VEGFR‐2 at an IC50 value of 0.10 µM, which is equipotent to sorafenib. Compound 14 inhibited VEGFR‐2 at an IC50 value of 0.11 µM, which is nearly equipotent to sorafenib. The tested compounds have more selectivity against cancer cell lines. Compounds 18, 10, 13, 11, and 14 are, respectively, 16.76, 9.24, 6.06, 2.78, and 2.85 times more toxic in HePpG2 cancer cells than in VERO normal cells. Also, compounds 18, 10, 13, 11, and 14 are, respectively, 14.07, 8.02, 2.81, 3.18, and 2.20 times more toxic in MCF‐7 than in VERO normal cells. The most active compounds, 10, 13, and 18, showed a good ADMET (absorption, distribution, metabolism, excretion, and toxicity) profile.
Twenty new N‐substituted‐4‐phenylphthalazin‐1‐amine derivatives were designed, synthesized, and e... more Twenty new N‐substituted‐4‐phenylphthalazin‐1‐amine derivatives were designed, synthesized, and evaluated for their anticancer activities against HepG2, HCT‐116, and MCF‐7 cells as VEGFR‐2 inhibitors. HCT‐116 was the most sensitive cell line to the influence of the new derivatives. In particular, compound 7f was found to be the most potent derivative among all the tested compounds against the three cancer cell lines, with 50% inhibition concentration, IC50 = 3.97, 4.83, and 4.58 µM, respectively, which is more potent than both sorafenib (IC50 = 9.18, 5.47, and 7.26 µM, respectively) and doxorubicin (IC50 = 7.94, 8.07, and 6.75 µM, respectively). Fifteen of the synthesized derivatives were selected to evaluate their inhibitory activities against VEGFR‐2. Compound 7f was found to be the most potent derivative that inhibited VEGFR‐2 at an IC50 value of 0.08 µM, which is more potent than sorafenib (IC50 = 0.10 µM). Compound 8c inhibited VEGFR‐2 at an IC50 value of 0.10 µM, which is equipotent to sorafenib. Moreover, compound 7a showed very good activity with IC50 values of 0.11 µM, which is nearly equipotent to sorafenib. In addition, compounds 7d, 7c, and 7g possessed very good VEGFR‐2‐inhibitory activity, with IC50 values of 0.14, 0.17, and 0.23 µM, respectively.
VEGF/VEGFR2 pathway is the crucial therapeutic target in the treatment of cancer. So that, a new ... more VEGF/VEGFR2 pathway is the crucial therapeutic target in the treatment of cancer. So that, a new series of quinoxaline-2(1H)-one derivatives were designed and synthesized. The synthesized compounds were tested against three human cancer cell lines (HepG-2, MCF-7 and HCT-116) aiming to evaluate its anti-proliferative activities. Doxorubicin as a universal anticancer drug and sorafenib as a potent VEGFR-2 inhibitor were used as positive controls. The data obtained from biological activity were found highly correlated with that obtained from molecular modeling studies. The most sensitive cell line to the influence of our new derivatives was HCT-116. Compounds 13b, 15, 16e and 17b exert the highest cytotoxic activities against the tested cell lines. Overall, compound 15 was the most active member with IC50 values of 5.30, 2.20, 5.50 µM against HepG-2, MCF-7 and HCT-116, respectively. Compounds 15 and 17b showed better anti-proliferative activities than doxorubicin and sorafenib against the three cancer cell lines. Additionally, compound 16e showed better anti-proliferative activities than doxorubicin and sorafenib against HepG-2 and HCT-116 but exhibited lower activity against MCF-7 cell line. In addition, the most promising members were further evaluated for their inhibitory activities against VEGFR-2. Compounds 15 and 17b potently inhibited VEGFR-2 at lower IC50 values of 1.09 and 1.19 µM, respectively, compared to sorafenib (IC50 = 1.27 µM). Moreover, docking studies were conducted to investigate the binding pattern of the synthesized compounds against the prospective molecular target VEGFR-2.
In view of their DNA intercalation activities as anticancer agents, novel fifteen [1,2,4]triazolo... more In view of their DNA intercalation activities as anticancer agents, novel fifteen [1,2,4]triazolo[4,3-c]quinazoline and bis([1,2,4]triazolo)[4,3-a:4',3'-c]quinazoline derivatives have been designed, synthesized and evaluated against HepG2 and HCT-116. The molecular design was performed to investigate the binding mode of the proposed compounds with DNA active site. The data obtained from biological testing highly correlated with that obtained from molecular modeling studies. HCT-116 was found to be more sensitive cell lines to the influence of the new derivatives. In particular, compounds 16, 18, 11 and 5 were found to be the most potent derivatives with IC50 = 3.61, 6.72, 7.16 and 5.18 µM respectively against HepG2 cell line. Also, compounds 16, 18, 11 and 5 displayed IC50 = 2.85, 3.82, 4.97 and 6.40 µM respectively against HCT-116 cell line. These derivatives displayed higher activities than doxorubicin, (IC50 = 7.94 and 8.07 µM respectively) against the two HepG2 and HCT-116 cell lines. The most active anti-proliferative derivatives 5, 6, 10, 11, 13, 16, 18, 19 and 20 were further evaluated for their DNA-binding affinity which revealed the ability of these compounds to intercalate DNA. The tested compounds displayed very strong to moderate DNA-binding affinities. Compounds 16 and 18 potently intercalate DNA at IC50 values of 26.03 and 28.37 µM respectively which were lower than IC50 of Doxorubicin (IC50 = 31.27). This finding indicated that these derivatives exhibited higher DNA binding activities than Doxorubicin. Also, compounds 11 and 5 displayed very strong DNA binding at IC50 = 30.84 and 33.56 µM respectively, which were nearly equipotent to that of doxorubicin. Moreover, most of our derivatives exhibited good ADMET profile.
Novel series of diazepam bearing sulfonamide moieties 5a-f and 7a-c were designed, synthesized an... more Novel series of diazepam bearing sulfonamide moieties 5a-f and 7a-c were designed, synthesized and evaluated for anticancer activity against HepG2, HCT-116 and MCF-7 cell lines. MCF-7 was the most sensitive cell line to the influence of the new derivatives. In particular, compound 5d was found to be the most potent derivative overall the tested compounds against the three HepG2, HCT116 and MCF-7 cancer cell lines with IC50 = 8.98 ± 0.1, 7.77 ± 0.1 and 6.99 ± 0.1 µM respectively. Compound 5d exhibited higher activity than sorafenib, (IC50 = 9.18 ± 0.6, 5.47 ± 0.3 and 7.26 ± 0.3 µM respectively), against HepG2 and MCF-7 but exhibited lower activity against HCT116 cancer cell lines respectively. Also, this compound displayed lower activity than doxorubicin, (IC50 = 7.94 ± 0.6, 8.07 ± 0.8 and 6.75 ± 0.4 µM respectively), against HepG2 and MCF-7 but higher activity against HCT116 cell lines respectively. Compounds 5b, 5c, 5d, 5e, 5f and 7c are respectively, 5.77, 8.58, 9.54, 5.71, 4.68 and 2.31 fold times more toxic in breast cancer cell lines (MCF-7, the most sensitive cells) than in VERO normal cells. All the synthesized compounds 5a-f and 7a-c were evaluated for their inhibitory activities against VEGFR-2. Among them, compound 5d was found to be the most potent derivative that inhibited VEGFR-2 at IC50 value of 0.10 ± 0.01 µM, which is equipotent to sorafenib IC50 value (0.10 ± 0.02 µM). Compound 5c exhibited excellent activity with IC50 value of 0.12 ± 0.01 µM which nearly equipotent to that of sorafenib. Compounds 5b, 5e and 5f exhibited very good activity with the same IC50 value of 0.14 ± 0.02 µM. Also, compounds 7c and 7b possessed good VEGFR-2 inhibition with IC50 values of 0.16 ± 0.06 and 0.17 ± 0.06 µM respectively which are more than the half activity of that of sorafenib. The data obtained from docking studies were highly correlated with that obtained from the biological screening.
A novel series of benzoxazole/benzothiazole derivatives 4a–c–11a–e were designed, synthesized, an... more A novel series of benzoxazole/benzothiazole derivatives 4a–c–11a–e were designed, synthesized, and evaluated for anticancer activity against HepG2, HCT‐116, and MCF‐7 cells. HCT‐116 was the most sensitive cell line to the influence of the new derivatives. In particular, compound 4c was found to be the most potent derivative against HepG2, HCT‐116, and MCF‐7 cells, with IC50 values = 9.45 ± 0.8, 5.76 ± 0.4, and 7.36 ± 0.5 µM, respectively. Compounds 4b, 9f, and 9c showed the highest anticancer activities against HepG2 cells with IC50 values of 9.97 ± 0.8, 9.99 ± 0.8, and 11.02 ± 1.0 µM, respectively, HCT‐116 cells with IC50 values of 6.99 ± 0.5, 7.44 ± 0.4, and 8.15 ± 0.8 µM, respectively, and MCF‐7 cells with IC50 values of 7.89 ± 0.7, 8.24 ± 0.7, and 9.32 ± 0.7 µM, respectively, in comparison with sorafenib as reference drug with IC50 values of 9.18 ± 0.6, 5.47 ± 0.3, and 7.26 ± 0.3 µM, respectively. The most active compounds 4a–c, 9b,c,e,f,h, and 11c,e were further evaluated for their VEGFR‐2 inhibition. Compounds 4c and 4b potently inhibited VEGFR‐2 at IC50 values of 0.12 ± 0.01 and 0.13 ± 0.02 µM, respectively, which are nearly equipotent to the sorafenib IC50 value (0.10 ± 0.02 µM). Furthermore, molecular docking studies were performed for all synthesized compounds to assess their binding pattern and affinity toward the VEGFR‐2 active site.
A new series of 4-acetyl-1-substituted-3,4-dihydroquinoxalin-2(1H)-ones (3–14) were designed and ... more A new series of 4-acetyl-1-substituted-3,4-dihydroquinoxalin-2(1H)-ones (3–14) were designed and synthesized in order to evaluate their α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-receptor antagonism as a proposed mode of their anticonvulsant activity. The structure of the synthesized compounds was confirmed by elemental analysis and spectral data (infrared, 1H nuclear magnetic resonance (NMR), 13CNMR, and mass). The molecular design was performed for all synthesized compounds to predict their binding affinity towards AMPA-receptor in order to rationalize their anticonvulsant activity in a qualitative way and explain the possible interactions that might take place between the tested derivatives and AMPA receptor in comparing to compounds III and YM872 in order to obtain the anticonvulsant effect. The data obtained from the molecular modeling was strongly correlated with that obtained from the biological screening which revealed that; compounds 14b, 14a, and 13b showed the highest binding affinities toward AMPA-receptor and also showed the highest anticonvulsant activities against pentylenetetrazole-induced seizures in experimental mice. The relative potencies of these compounds were 1.89, 1.83, and 1.51 respectively, in comparing to diazepam.
Newly designed thiazolidine-2,4-diones 3–7a–c were synthesized, and their anticancer activities w... more Newly designed thiazolidine-2,4-diones 3–7a–c were synthesized, and their anticancer activities were screened against three cancer lines. They showed potent activities against HepG2 compared to the other HCT116 and MCF-7 tumor cell lines. Compounds 7c and 6c were detected as highly effective derivatives against MCF-7 (IC50 = 7.78 and 8.15 µM), HCT116 (IC50 = 5.77 and 7.11 µM) and HepG2 (IC50 = 8.82 and 8.99 µM). The highly effective derivatives 6a–c and 7a–c were tested against VERO normal cell lines. All derivatives were evaluated for their VEGFR-2 inhibitory actions and demonstrated high to low activities, with IC50 values varying from 0.08 to 0.93 µM. Moreover, derivatives 5a–c, 6a–c and 7a–c were assessed to verify their in vitro binding affinities to PPARγ and insulin-secreting activities. Finally, docking studies were performed to explore their affinities and binding modes toward both VEGFR-2 and PPARγ receptors.
The lack of effective therapies for epileptic patients and the potentially harmful consequences o... more The lack of effective therapies for epileptic patients and the potentially harmful consequences of untreated seizure incidents have made epileptic disorders in humans a major health concern. Therefore, new and more potent anticonvulsant drugs are continually sought after, to combat epilepsy. On the basis of the pharmacophoric structural specifications of effective α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) antagonists with an efficient anticonvulsant activity, the present work reports the design and synthesis of two novel sets of quinoxaline derivatives. The anticonvulsant activity of the synthesized compounds was evaluated in vivo according to the pentylenetetrazol‐induced seizure protocol, and the results were compared with those of perampanel as a reference drug. Among the synthesized compounds, 24, 28, 32, and 33 showed promising activities with ED50 values of 37.50, 23.02, 29.16, and 23.86 mg/kg, respectively. Docking studies of these compounds suggested that AMPA binding could be the mechanism of action of these derivatives. Overall, the pharmacophore‐based structural optimization, in vivo and in silico docking, and druglikeness studies indicated that the designed compounds could serve as promising candidates for the development of effective anticonvulsant agents with good pharmacokinetic profiles.
Novel triazoloquinazolines were designed and synthesized and evaluated as anticancer agents again... more Novel triazoloquinazolines were designed and synthesized and evaluated as anticancer agents against HepG2 and HCT-116 cells. The biological testing data corresponded well to those of the molecular docking studies. The HCT-116 cell line was most affected due to the actions of our derivatives. Derivative 7a was the most potent one against both HepG2 and HCT116 cells, with IC50 = 7.98 and 5.57 µM, respectively. This compound showed anticancer activity that was nearly equipotent to that of doxorubicin against HepG2 cells, but higher than that of doxorubicin against HCT116 cells (IC50 = 7.94 and 8.07 µM, respectively). Compounds 8, 7b , and 6f showed excellent anticancer activities against both the HCT116 and HepG2 cell lines. The highly active compounds 6f , 7a , 7b , and 8 were evaluated for their DNA-binding activities. Compounds 7a and 8 showed the highest binding activities. These derivatives potently intercalate in DNA, at IC50 values of 42.90 and 48.13 µM, respectively. Derivatives 6f and 7b showed good DNA-binding activities, with IC50 values of 54.24 and 50.56 µM, respectively. Furthermore, in silico calculated ADMET profiles were established for our four highly active derivatives, in comparison to doxorubicin. Our derivatives 6f , 7a , 7b , and 8 showed a very good ADMET profile. Compounds 6f , 7a , 7b , and 8 follow Lipinski's rules, while doxorubicin violates three of these rules.
Eleven novel [1,2,4]triazolo[4,3-c]quinazolines were designed, synthesized, and evaluated against... more Eleven novel [1,2,4]triazolo[4,3-c]quinazolines were designed, synthesized, and evaluated against HepG2 and HCT-116 cells. The molecular design was performed to investigate the binding mode of the proposed compounds with the DNA active site. The data obtained from biological testing highly correlated with that obtained from molecular modeling. HCT-116 was found to be the most sensitive cell line to the influence of the new derivatives. In particular, compounds 6f and 6e were found to be the most potent derivatives over all the tested compounds against the two HepG2 and HCT116 cancer cell lines, with IC50 = 23.44 ± 2.9, 12.63 ± 1.2, and 25.80 ± 2.1, and 14.32 ± 1.5 µM, respectively. Although compounds 6f and 6e displayed less activity than doxorubicin (IC50 = 7.94 ± 0.6 and 8.07 ± 0.8 µM, respectively), both could be useful as a template for future design, optimization, and investigation to produce more potent anticancer analogs. The most active derivatives 6a , 6c , 6e , and 6f were evaluated for their DNA-binding activities. Compound 6f displayed the highest binding affinity. This compound potently intercalates DNA at a decreased IC50 value (54.08 µM). Compounds 6a , 6c , and 6e exhibited good DNA-binding affinities, with IC50 values of 79.35, 84.08, and 59.35 µM, respectively. Furthermore, ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiles were calculated for the four most active compounds in comparison to doxorubicin as a reference drug. Our derivatives 6a , 6c , 6e , and 6f displayed very good in-silico-predicted ADMET profiles. Doxorubicin violates three of Lipinski's rules, our derivatives 6a , 6c , 6e , and 6f do not violate any rule.
Novel pyridine‐derived compounds (5–19) were designed and synthesized, and their anticancer activ... more Novel pyridine‐derived compounds (5–19) were designed and synthesized, and their anticancer activities were evaluated against HepG2 and MCF‐7 cells, targeting the VEGFR‐2 enzyme. Compounds 10, 9, 8, and 15 were found to be the most potent derivatives against the two cancer cell lines, HepG2 and MCF‐7, respectively, with IC50 = 4.25 and 6.08 µM, 4.68 and 11.06 µM, 4.34 and 10.29 µM, and 6.37 and 12.83 µM. Compound 10 displayed higher activity against HepG2 cells than sorafenib (IC50 = 9.18 and 5.47 µM, respectively) and doxorubicin (IC50 = 7.94 and 8.07 µM, respectively). It also showed higher activity than doxorubicin against MCF‐7 cells, but lower activity than sorafenib. Compounds 9, 8, and 15 displayed higher activities than sorafenib and doxorubicin against HepG2 cells but exhibited lower activities against MCF‐7 cells. Compound 10 potently inhibited VEGFR‐2 at an IC50 value of 0.12 µM, which is nearly equipotent to sorafenib (IC50 = 0.10 µM). Compounds 8 and 9 exhibited very good activity with the same IC50 value of 0.13 µM. The six most potent derivatives, 6, 9, 8, 10, 15, and 18, were tested for their cytotoxicity against normal Vero cells. Compounds 6, 8, 9, 10, 15, and 18 are, respectively, 1.13, 3.74, 4.18, 3.64, 2.81, and 2.00 times more toxic to HepG2 and 2.06, 1.58, 1.76, 2.54, 1.40, and 2.69 times more toxic to MCF‐7 breast cancer cells than in normal Vero cells.
The resistance of pathogenic microbes to currently available antimicrobial agents has been consid... more The resistance of pathogenic microbes to currently available antimicrobial agents has been considered a global alarming concern.
The anticancer activity of novel thiazolidine‐2,4‐diones was evaluated against HepG2, HCT‐116, an... more The anticancer activity of novel thiazolidine‐2,4‐diones was evaluated against HepG2, HCT‐116, and MCF‐7 cells. MCF‐7 was the most sensitive cell line to the cytotoxicity of the new derivatives. In particular, compounds 18, 12, 17, and 16 were found to be the most potent derivatives over all the tested compounds against the cancer cell lines HepG2, HCT116, and MCF‐7, with IC50 = 9.16 ± 0.9, 8.98 ± 0.7, 5.49 ± 0.5 µM; 9.19 ± 0.5, 8.40 ± 0.7, 6.10 ± 0.4 µM; 10.78 ± 1.2, 8.87 ± 1.5, 7.08 ± 1.6 µM; and 10.87 ± 0.8, 9.05 ± 0.7, 7.32 ± 0.4 µM, respectively. Compounds 18 and 12 have nearly the same activities as sorafenib (IC50 = 9.18 ± 0.6, 5.47 ± 0.3, and 7.26 ± 0.3 µM, respectively), against HepG2 cells, but slightly lower activity against HCT116 cells and slightly higher activity against the MCF‐7 cancer cell line. Also, these compounds displayed lower activities than doxorubicin against HepG2 and HCT‐116 cells but higher activity against MCF‐7 cells (IC50 = 7.94 ± 0.6, 8.07 ± 0.8, and 6.75 ± 0.4 µM, respectively). In contrast, compounds 17 and 16 exhibited lower activities than sorafenib against HepG2 and HCT116 cells, but nearly equipotent activity against the MCF‐7 cancer cell line. Also, these compounds displayed lower activities than doxorubicin against the three cell lines. All the synthesized derivatives 7–18 were evaluated for their inhibitory activities against VEGFR‐2. The tested compounds displayed high to medium inhibitory activity, with IC50 values ranging from 0.17 ± 0.02 to 0.27 ± 0.03 µM. Compounds 18, 12, 17, and 16 potently inhibited VEGFR‐2 at IC50 values of 0.17 ± 0.02, 0.17 ± 0.02, 0.18 ± 0.02, and 0.18 ± 0.02 µM, respectively, which are nearly more than half of that of the IC50 value for sorafenib (0.10 ± 0.02 µM).
A novel series of 5‐(4‐methoxybenzylidene)thiazolidine‐2,4‐dione derivatives, 5a–g and 7a–f, was ... more A novel series of 5‐(4‐methoxybenzylidene)thiazolidine‐2,4‐dione derivatives, 5a–g and 7a–f, was designed, synthesized, and evaluated for their anticancer activity against HepG2, HCT116, and MCF‐7 cells. HepG2 and HCT116 were the most sensitive cell lines to the influence of the new derivatives. In particular, compounds 7f, 7e, 7d, and 7c were found to be the most potent derivatives of all the tested compounds against the HepG2, HCT116, and MCF‐7 cancer cell lines. Compound 7f (IC50 = 6.19 ± 0.5, 5.47 ± 0.3, and 7.26 ± 0.3 µM, respectively) exhibited a higher activity than sorafenib (IC50 = 9.18 ± 0.6, 8.37 ± 0.7, and 5.10 ± 0.4 µM, respectively) against HepG2 and MCF‐7, cells but a lower activity against HCT116 cancer cells, respectively. Also, this compound displayed a higher activity than doxorubicin (IC50 = 7.94 ± 0.6, 8.07 ± 0.8, and 6.75 ± 0.4 µM, respectively) against HepG2 and MCF‐7 cells, but nearly the same activity against HCT116 cells, respectively. All derivatives, 5a–g and 7a–f, were evaluated for their inhibitory activities against vascular endothelial growth factor receptor‐2 (VEGFR‐2). Among them, compound 7f was found to be the most potent derivative that inhibited VEGFR‐2 at an IC50 value of 0.12 ± 0.02 µM, which is nearly the same as that of sorafenib (IC50 = 0.10 ± 0.02 µM). Compounds 7e, 7d, 7c, and 7b exhibited the highest activity, with IC50 values of 0.13 ± 0.02, 0.14 ± 0.02, 0.14 ± 0.02, and 0.18 ± 0.03 µM, respectively, which are more than the half of that of sorafenib. Furthermore, molecular docking was performed to investigate their binding mode and affinities toward the VEGFR‐2 receptor. The data obtained from the docking studies highly correlated with those obtained from the biological screening.
Thirteen novel [1,2,4]triazolo[4,3-c]quinazoline derivatives as DNA intercalators were synthesize... more Thirteen novel [1,2,4]triazolo[4,3-c]quinazoline derivatives as DNA intercalators were synthesized and their anticancer activities evaluated against HepG2 and HCT-116 cells. A docking study was carried out to explore how the new derivatives bind to active sites of DNA. The docking data were highly interrelated with that of biological testing. The HCT-116 cell line was the most sensitive one to the effect of the new derivatives. Compound 7c exhibited the highest anticancer activities against both the HepG2 and HCT116 cancer cell lines. Despite this compound displaying less activity than doxorubicin, it could be useful as a template for future manipulation, optimization, and investigation to produce other analogs with potential activity. The most active derivatives, 7c , 7b , and 7a were evaluated as DNA binders. Compound 7c displayed the highest binding affinity. Furthermore, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) profile was calculated for the four most active compounds in comparison to doxorubicin as reference drug. Our derivatives 7a , 7b , and 7c displayed a very good calculated ADMET profile in comparison to doxorubicin.
Novel heterocyclic derivatives (4–22) were designed, synthesized, and evaluated against hepatocel... more Novel heterocyclic derivatives (4–22) were designed, synthesized, and evaluated against hepatocellular carcinoma type (HepG2) and breast cancer (MCF‐7) cells, targeting the VEGFR‐2 enzyme. Compounds 18, 10, 13, 11, and 14 were found to be the most potent derivatives against both the HepG2 and MCF‐7 cancer cell lines, with GI50 = 2.11, 2.54 µM, 3.16, 3.64 µM, 3.24, 6.99 µM, 7.41, 6.49 µM and 8.08, 10.46 µM, respectively. Compounds 18 and 10 showed higher activities against both HepG2 and MCF‐7 cells than sorafenib (GI50 = 9.18, 5.47 µM, respectively) and doxorubicin (GI50 = 7.94, 8.07 µM, respectively). Compounds 13, 11, and 14 showed higher activities than sorafenib against HepG2 cancer cells, but lower activities against MCF‐7 cells. Compounds 18, 13, and 10 were more potent than sorafenib, inhibiting vascular endothelial growth factor receptor‐2 (VEGFR‐2) at GI50 values of 0.05, 0.06, and 0.08 µM, respectively. Compound 11 inhibited VEGFR‐2 at an IC50 value of 0.10 µM, which is equipotent to sorafenib. Compound 14 inhibited VEGFR‐2 at an IC50 value of 0.11 µM, which is nearly equipotent to sorafenib. The tested compounds have more selectivity against cancer cell lines. Compounds 18, 10, 13, 11, and 14 are, respectively, 16.76, 9.24, 6.06, 2.78, and 2.85 times more toxic in HePpG2 cancer cells than in VERO normal cells. Also, compounds 18, 10, 13, 11, and 14 are, respectively, 14.07, 8.02, 2.81, 3.18, and 2.20 times more toxic in MCF‐7 than in VERO normal cells. The most active compounds, 10, 13, and 18, showed a good ADMET (absorption, distribution, metabolism, excretion, and toxicity) profile.
Twenty new N‐substituted‐4‐phenylphthalazin‐1‐amine derivatives were designed, synthesized, and e... more Twenty new N‐substituted‐4‐phenylphthalazin‐1‐amine derivatives were designed, synthesized, and evaluated for their anticancer activities against HepG2, HCT‐116, and MCF‐7 cells as VEGFR‐2 inhibitors. HCT‐116 was the most sensitive cell line to the influence of the new derivatives. In particular, compound 7f was found to be the most potent derivative among all the tested compounds against the three cancer cell lines, with 50% inhibition concentration, IC50 = 3.97, 4.83, and 4.58 µM, respectively, which is more potent than both sorafenib (IC50 = 9.18, 5.47, and 7.26 µM, respectively) and doxorubicin (IC50 = 7.94, 8.07, and 6.75 µM, respectively). Fifteen of the synthesized derivatives were selected to evaluate their inhibitory activities against VEGFR‐2. Compound 7f was found to be the most potent derivative that inhibited VEGFR‐2 at an IC50 value of 0.08 µM, which is more potent than sorafenib (IC50 = 0.10 µM). Compound 8c inhibited VEGFR‐2 at an IC50 value of 0.10 µM, which is equipotent to sorafenib. Moreover, compound 7a showed very good activity with IC50 values of 0.11 µM, which is nearly equipotent to sorafenib. In addition, compounds 7d, 7c, and 7g possessed very good VEGFR‐2‐inhibitory activity, with IC50 values of 0.14, 0.17, and 0.23 µM, respectively.
VEGF/VEGFR2 pathway is the crucial therapeutic target in the treatment of cancer. So that, a new ... more VEGF/VEGFR2 pathway is the crucial therapeutic target in the treatment of cancer. So that, a new series of quinoxaline-2(1H)-one derivatives were designed and synthesized. The synthesized compounds were tested against three human cancer cell lines (HepG-2, MCF-7 and HCT-116) aiming to evaluate its anti-proliferative activities. Doxorubicin as a universal anticancer drug and sorafenib as a potent VEGFR-2 inhibitor were used as positive controls. The data obtained from biological activity were found highly correlated with that obtained from molecular modeling studies. The most sensitive cell line to the influence of our new derivatives was HCT-116. Compounds 13b, 15, 16e and 17b exert the highest cytotoxic activities against the tested cell lines. Overall, compound 15 was the most active member with IC50 values of 5.30, 2.20, 5.50 µM against HepG-2, MCF-7 and HCT-116, respectively. Compounds 15 and 17b showed better anti-proliferative activities than doxorubicin and sorafenib against the three cancer cell lines. Additionally, compound 16e showed better anti-proliferative activities than doxorubicin and sorafenib against HepG-2 and HCT-116 but exhibited lower activity against MCF-7 cell line. In addition, the most promising members were further evaluated for their inhibitory activities against VEGFR-2. Compounds 15 and 17b potently inhibited VEGFR-2 at lower IC50 values of 1.09 and 1.19 µM, respectively, compared to sorafenib (IC50 = 1.27 µM). Moreover, docking studies were conducted to investigate the binding pattern of the synthesized compounds against the prospective molecular target VEGFR-2.
In view of their DNA intercalation activities as anticancer agents, novel fifteen [1,2,4]triazolo... more In view of their DNA intercalation activities as anticancer agents, novel fifteen [1,2,4]triazolo[4,3-c]quinazoline and bis([1,2,4]triazolo)[4,3-a:4',3'-c]quinazoline derivatives have been designed, synthesized and evaluated against HepG2 and HCT-116. The molecular design was performed to investigate the binding mode of the proposed compounds with DNA active site. The data obtained from biological testing highly correlated with that obtained from molecular modeling studies. HCT-116 was found to be more sensitive cell lines to the influence of the new derivatives. In particular, compounds 16, 18, 11 and 5 were found to be the most potent derivatives with IC50 = 3.61, 6.72, 7.16 and 5.18 µM respectively against HepG2 cell line. Also, compounds 16, 18, 11 and 5 displayed IC50 = 2.85, 3.82, 4.97 and 6.40 µM respectively against HCT-116 cell line. These derivatives displayed higher activities than doxorubicin, (IC50 = 7.94 and 8.07 µM respectively) against the two HepG2 and HCT-116 cell lines. The most active anti-proliferative derivatives 5, 6, 10, 11, 13, 16, 18, 19 and 20 were further evaluated for their DNA-binding affinity which revealed the ability of these compounds to intercalate DNA. The tested compounds displayed very strong to moderate DNA-binding affinities. Compounds 16 and 18 potently intercalate DNA at IC50 values of 26.03 and 28.37 µM respectively which were lower than IC50 of Doxorubicin (IC50 = 31.27). This finding indicated that these derivatives exhibited higher DNA binding activities than Doxorubicin. Also, compounds 11 and 5 displayed very strong DNA binding at IC50 = 30.84 and 33.56 µM respectively, which were nearly equipotent to that of doxorubicin. Moreover, most of our derivatives exhibited good ADMET profile.
Novel series of diazepam bearing sulfonamide moieties 5a-f and 7a-c were designed, synthesized an... more Novel series of diazepam bearing sulfonamide moieties 5a-f and 7a-c were designed, synthesized and evaluated for anticancer activity against HepG2, HCT-116 and MCF-7 cell lines. MCF-7 was the most sensitive cell line to the influence of the new derivatives. In particular, compound 5d was found to be the most potent derivative overall the tested compounds against the three HepG2, HCT116 and MCF-7 cancer cell lines with IC50 = 8.98 ± 0.1, 7.77 ± 0.1 and 6.99 ± 0.1 µM respectively. Compound 5d exhibited higher activity than sorafenib, (IC50 = 9.18 ± 0.6, 5.47 ± 0.3 and 7.26 ± 0.3 µM respectively), against HepG2 and MCF-7 but exhibited lower activity against HCT116 cancer cell lines respectively. Also, this compound displayed lower activity than doxorubicin, (IC50 = 7.94 ± 0.6, 8.07 ± 0.8 and 6.75 ± 0.4 µM respectively), against HepG2 and MCF-7 but higher activity against HCT116 cell lines respectively. Compounds 5b, 5c, 5d, 5e, 5f and 7c are respectively, 5.77, 8.58, 9.54, 5.71, 4.68 and 2.31 fold times more toxic in breast cancer cell lines (MCF-7, the most sensitive cells) than in VERO normal cells. All the synthesized compounds 5a-f and 7a-c were evaluated for their inhibitory activities against VEGFR-2. Among them, compound 5d was found to be the most potent derivative that inhibited VEGFR-2 at IC50 value of 0.10 ± 0.01 µM, which is equipotent to sorafenib IC50 value (0.10 ± 0.02 µM). Compound 5c exhibited excellent activity with IC50 value of 0.12 ± 0.01 µM which nearly equipotent to that of sorafenib. Compounds 5b, 5e and 5f exhibited very good activity with the same IC50 value of 0.14 ± 0.02 µM. Also, compounds 7c and 7b possessed good VEGFR-2 inhibition with IC50 values of 0.16 ± 0.06 and 0.17 ± 0.06 µM respectively which are more than the half activity of that of sorafenib. The data obtained from docking studies were highly correlated with that obtained from the biological screening.
A novel series of benzoxazole/benzothiazole derivatives 4a–c–11a–e were designed, synthesized, an... more A novel series of benzoxazole/benzothiazole derivatives 4a–c–11a–e were designed, synthesized, and evaluated for anticancer activity against HepG2, HCT‐116, and MCF‐7 cells. HCT‐116 was the most sensitive cell line to the influence of the new derivatives. In particular, compound 4c was found to be the most potent derivative against HepG2, HCT‐116, and MCF‐7 cells, with IC50 values = 9.45 ± 0.8, 5.76 ± 0.4, and 7.36 ± 0.5 µM, respectively. Compounds 4b, 9f, and 9c showed the highest anticancer activities against HepG2 cells with IC50 values of 9.97 ± 0.8, 9.99 ± 0.8, and 11.02 ± 1.0 µM, respectively, HCT‐116 cells with IC50 values of 6.99 ± 0.5, 7.44 ± 0.4, and 8.15 ± 0.8 µM, respectively, and MCF‐7 cells with IC50 values of 7.89 ± 0.7, 8.24 ± 0.7, and 9.32 ± 0.7 µM, respectively, in comparison with sorafenib as reference drug with IC50 values of 9.18 ± 0.6, 5.47 ± 0.3, and 7.26 ± 0.3 µM, respectively. The most active compounds 4a–c, 9b,c,e,f,h, and 11c,e were further evaluated for their VEGFR‐2 inhibition. Compounds 4c and 4b potently inhibited VEGFR‐2 at IC50 values of 0.12 ± 0.01 and 0.13 ± 0.02 µM, respectively, which are nearly equipotent to the sorafenib IC50 value (0.10 ± 0.02 µM). Furthermore, molecular docking studies were performed for all synthesized compounds to assess their binding pattern and affinity toward the VEGFR‐2 active site.
A new series of 4-acetyl-1-substituted-3,4-dihydroquinoxalin-2(1H)-ones (3–14) were designed and ... more A new series of 4-acetyl-1-substituted-3,4-dihydroquinoxalin-2(1H)-ones (3–14) were designed and synthesized in order to evaluate their α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-receptor antagonism as a proposed mode of their anticonvulsant activity. The structure of the synthesized compounds was confirmed by elemental analysis and spectral data (infrared, 1H nuclear magnetic resonance (NMR), 13CNMR, and mass). The molecular design was performed for all synthesized compounds to predict their binding affinity towards AMPA-receptor in order to rationalize their anticonvulsant activity in a qualitative way and explain the possible interactions that might take place between the tested derivatives and AMPA receptor in comparing to compounds III and YM872 in order to obtain the anticonvulsant effect. The data obtained from the molecular modeling was strongly correlated with that obtained from the biological screening which revealed that; compounds 14b, 14a, and 13b showed the highest binding affinities toward AMPA-receptor and also showed the highest anticonvulsant activities against pentylenetetrazole-induced seizures in experimental mice. The relative potencies of these compounds were 1.89, 1.83, and 1.51 respectively, in comparing to diazepam.
Newly designed thiazolidine-2,4-diones 3–7a–c were synthesized, and their anticancer activities w... more Newly designed thiazolidine-2,4-diones 3–7a–c were synthesized, and their anticancer activities were screened against three cancer lines. They showed potent activities against HepG2 compared to the other HCT116 and MCF-7 tumor cell lines. Compounds 7c and 6c were detected as highly effective derivatives against MCF-7 (IC50 = 7.78 and 8.15 µM), HCT116 (IC50 = 5.77 and 7.11 µM) and HepG2 (IC50 = 8.82 and 8.99 µM). The highly effective derivatives 6a–c and 7a–c were tested against VERO normal cell lines. All derivatives were evaluated for their VEGFR-2 inhibitory actions and demonstrated high to low activities, with IC50 values varying from 0.08 to 0.93 µM. Moreover, derivatives 5a–c, 6a–c and 7a–c were assessed to verify their in vitro binding affinities to PPARγ and insulin-secreting activities. Finally, docking studies were performed to explore their affinities and binding modes toward both VEGFR-2 and PPARγ receptors.
The lack of effective therapies for epileptic patients and the potentially harmful consequences o... more The lack of effective therapies for epileptic patients and the potentially harmful consequences of untreated seizure incidents have made epileptic disorders in humans a major health concern. Therefore, new and more potent anticonvulsant drugs are continually sought after, to combat epilepsy. On the basis of the pharmacophoric structural specifications of effective α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) antagonists with an efficient anticonvulsant activity, the present work reports the design and synthesis of two novel sets of quinoxaline derivatives. The anticonvulsant activity of the synthesized compounds was evaluated in vivo according to the pentylenetetrazol‐induced seizure protocol, and the results were compared with those of perampanel as a reference drug. Among the synthesized compounds, 24, 28, 32, and 33 showed promising activities with ED50 values of 37.50, 23.02, 29.16, and 23.86 mg/kg, respectively. Docking studies of these compounds suggested that AMPA binding could be the mechanism of action of these derivatives. Overall, the pharmacophore‐based structural optimization, in vivo and in silico docking, and druglikeness studies indicated that the designed compounds could serve as promising candidates for the development of effective anticonvulsant agents with good pharmacokinetic profiles.
Novel triazoloquinazolines were designed and synthesized and evaluated as anticancer agents again... more Novel triazoloquinazolines were designed and synthesized and evaluated as anticancer agents against HepG2 and HCT-116 cells. The biological testing data corresponded well to those of the molecular docking studies. The HCT-116 cell line was most affected due to the actions of our derivatives. Derivative 7a was the most potent one against both HepG2 and HCT116 cells, with IC50 = 7.98 and 5.57 µM, respectively. This compound showed anticancer activity that was nearly equipotent to that of doxorubicin against HepG2 cells, but higher than that of doxorubicin against HCT116 cells (IC50 = 7.94 and 8.07 µM, respectively). Compounds 8, 7b , and 6f showed excellent anticancer activities against both the HCT116 and HepG2 cell lines. The highly active compounds 6f , 7a , 7b , and 8 were evaluated for their DNA-binding activities. Compounds 7a and 8 showed the highest binding activities. These derivatives potently intercalate in DNA, at IC50 values of 42.90 and 48.13 µM, respectively. Derivatives 6f and 7b showed good DNA-binding activities, with IC50 values of 54.24 and 50.56 µM, respectively. Furthermore, in silico calculated ADMET profiles were established for our four highly active derivatives, in comparison to doxorubicin. Our derivatives 6f , 7a , 7b , and 8 showed a very good ADMET profile. Compounds 6f , 7a , 7b , and 8 follow Lipinski's rules, while doxorubicin violates three of these rules.
Eleven novel [1,2,4]triazolo[4,3-c]quinazolines were designed, synthesized, and evaluated against... more Eleven novel [1,2,4]triazolo[4,3-c]quinazolines were designed, synthesized, and evaluated against HepG2 and HCT-116 cells. The molecular design was performed to investigate the binding mode of the proposed compounds with the DNA active site. The data obtained from biological testing highly correlated with that obtained from molecular modeling. HCT-116 was found to be the most sensitive cell line to the influence of the new derivatives. In particular, compounds 6f and 6e were found to be the most potent derivatives over all the tested compounds against the two HepG2 and HCT116 cancer cell lines, with IC50 = 23.44 ± 2.9, 12.63 ± 1.2, and 25.80 ± 2.1, and 14.32 ± 1.5 µM, respectively. Although compounds 6f and 6e displayed less activity than doxorubicin (IC50 = 7.94 ± 0.6 and 8.07 ± 0.8 µM, respectively), both could be useful as a template for future design, optimization, and investigation to produce more potent anticancer analogs. The most active derivatives 6a , 6c , 6e , and 6f were evaluated for their DNA-binding activities. Compound 6f displayed the highest binding affinity. This compound potently intercalates DNA at a decreased IC50 value (54.08 µM). Compounds 6a , 6c , and 6e exhibited good DNA-binding affinities, with IC50 values of 79.35, 84.08, and 59.35 µM, respectively. Furthermore, ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiles were calculated for the four most active compounds in comparison to doxorubicin as a reference drug. Our derivatives 6a , 6c , 6e , and 6f displayed very good in-silico-predicted ADMET profiles. Doxorubicin violates three of Lipinski's rules, our derivatives 6a , 6c , 6e , and 6f do not violate any rule.
Novel pyridine‐derived compounds (5–19) were designed and synthesized, and their anticancer activ... more Novel pyridine‐derived compounds (5–19) were designed and synthesized, and their anticancer activities were evaluated against HepG2 and MCF‐7 cells, targeting the VEGFR‐2 enzyme. Compounds 10, 9, 8, and 15 were found to be the most potent derivatives against the two cancer cell lines, HepG2 and MCF‐7, respectively, with IC50 = 4.25 and 6.08 µM, 4.68 and 11.06 µM, 4.34 and 10.29 µM, and 6.37 and 12.83 µM. Compound 10 displayed higher activity against HepG2 cells than sorafenib (IC50 = 9.18 and 5.47 µM, respectively) and doxorubicin (IC50 = 7.94 and 8.07 µM, respectively). It also showed higher activity than doxorubicin against MCF‐7 cells, but lower activity than sorafenib. Compounds 9, 8, and 15 displayed higher activities than sorafenib and doxorubicin against HepG2 cells but exhibited lower activities against MCF‐7 cells. Compound 10 potently inhibited VEGFR‐2 at an IC50 value of 0.12 µM, which is nearly equipotent to sorafenib (IC50 = 0.10 µM). Compounds 8 and 9 exhibited very good activity with the same IC50 value of 0.13 µM. The six most potent derivatives, 6, 9, 8, 10, 15, and 18, were tested for their cytotoxicity against normal Vero cells. Compounds 6, 8, 9, 10, 15, and 18 are, respectively, 1.13, 3.74, 4.18, 3.64, 2.81, and 2.00 times more toxic to HepG2 and 2.06, 1.58, 1.76, 2.54, 1.40, and 2.69 times more toxic to MCF‐7 breast cancer cells than in normal Vero cells.
The resistance of pathogenic microbes to currently available antimicrobial agents has been consid... more The resistance of pathogenic microbes to currently available antimicrobial agents has been considered a global alarming concern.
The anticancer activity of novel thiazolidine‐2,4‐diones was evaluated against HepG2, HCT‐116, an... more The anticancer activity of novel thiazolidine‐2,4‐diones was evaluated against HepG2, HCT‐116, and MCF‐7 cells. MCF‐7 was the most sensitive cell line to the cytotoxicity of the new derivatives. In particular, compounds 18, 12, 17, and 16 were found to be the most potent derivatives over all the tested compounds against the cancer cell lines HepG2, HCT116, and MCF‐7, with IC50 = 9.16 ± 0.9, 8.98 ± 0.7, 5.49 ± 0.5 µM; 9.19 ± 0.5, 8.40 ± 0.7, 6.10 ± 0.4 µM; 10.78 ± 1.2, 8.87 ± 1.5, 7.08 ± 1.6 µM; and 10.87 ± 0.8, 9.05 ± 0.7, 7.32 ± 0.4 µM, respectively. Compounds 18 and 12 have nearly the same activities as sorafenib (IC50 = 9.18 ± 0.6, 5.47 ± 0.3, and 7.26 ± 0.3 µM, respectively), against HepG2 cells, but slightly lower activity against HCT116 cells and slightly higher activity against the MCF‐7 cancer cell line. Also, these compounds displayed lower activities than doxorubicin against HepG2 and HCT‐116 cells but higher activity against MCF‐7 cells (IC50 = 7.94 ± 0.6, 8.07 ± 0.8, and 6.75 ± 0.4 µM, respectively). In contrast, compounds 17 and 16 exhibited lower activities than sorafenib against HepG2 and HCT116 cells, but nearly equipotent activity against the MCF‐7 cancer cell line. Also, these compounds displayed lower activities than doxorubicin against the three cell lines. All the synthesized derivatives 7–18 were evaluated for their inhibitory activities against VEGFR‐2. The tested compounds displayed high to medium inhibitory activity, with IC50 values ranging from 0.17 ± 0.02 to 0.27 ± 0.03 µM. Compounds 18, 12, 17, and 16 potently inhibited VEGFR‐2 at IC50 values of 0.17 ± 0.02, 0.17 ± 0.02, 0.18 ± 0.02, and 0.18 ± 0.02 µM, respectively, which are nearly more than half of that of the IC50 value for sorafenib (0.10 ± 0.02 µM).
A novel series of 5‐(4‐methoxybenzylidene)thiazolidine‐2,4‐dione derivatives, 5a–g and 7a–f, was ... more A novel series of 5‐(4‐methoxybenzylidene)thiazolidine‐2,4‐dione derivatives, 5a–g and 7a–f, was designed, synthesized, and evaluated for their anticancer activity against HepG2, HCT116, and MCF‐7 cells. HepG2 and HCT116 were the most sensitive cell lines to the influence of the new derivatives. In particular, compounds 7f, 7e, 7d, and 7c were found to be the most potent derivatives of all the tested compounds against the HepG2, HCT116, and MCF‐7 cancer cell lines. Compound 7f (IC50 = 6.19 ± 0.5, 5.47 ± 0.3, and 7.26 ± 0.3 µM, respectively) exhibited a higher activity than sorafenib (IC50 = 9.18 ± 0.6, 8.37 ± 0.7, and 5.10 ± 0.4 µM, respectively) against HepG2 and MCF‐7, cells but a lower activity against HCT116 cancer cells, respectively. Also, this compound displayed a higher activity than doxorubicin (IC50 = 7.94 ± 0.6, 8.07 ± 0.8, and 6.75 ± 0.4 µM, respectively) against HepG2 and MCF‐7 cells, but nearly the same activity against HCT116 cells, respectively. All derivatives, 5a–g and 7a–f, were evaluated for their inhibitory activities against vascular endothelial growth factor receptor‐2 (VEGFR‐2). Among them, compound 7f was found to be the most potent derivative that inhibited VEGFR‐2 at an IC50 value of 0.12 ± 0.02 µM, which is nearly the same as that of sorafenib (IC50 = 0.10 ± 0.02 µM). Compounds 7e, 7d, 7c, and 7b exhibited the highest activity, with IC50 values of 0.13 ± 0.02, 0.14 ± 0.02, 0.14 ± 0.02, and 0.18 ± 0.03 µM, respectively, which are more than the half of that of sorafenib. Furthermore, molecular docking was performed to investigate their binding mode and affinities toward the VEGFR‐2 receptor. The data obtained from the docking studies highly correlated with those obtained from the biological screening.
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