New compounds of 4-anilino-6-substituted quinazoline were designed, synthesized and tested for th... more New compounds of 4-anilino-6-substituted quinazoline were designed, synthesized and tested for their EGFR-TK and tumor growth inhibitory activities. The synthesized compounds were appended with amides 6 and 7, dithiocarbamate ester 8a–f or urea/thiourea 9–12 moieties at C-6 of the quinazoline ring to work as extra hydrogen bond acceptors. All the synthesized compounds were effective against EGFR-TK activity, particularly, derivatives 8a, 8f and 9 with IC50 values of 0.14±0.003, 0.119±0.003, and 0.115±0.002 μM, respectively, showed the best activities. The three compounds were further assayed for their cytotoxicity against MCF-7, H-69, SKOV-3 and LS-174T cell lines. Multikinase enzymes inhibition activity of compound 9 was further screened including VEGFR-2, c-MER, c-MET and Her-2. Compounds 8a, 8f, and 9 were docked into the ATP binding site of EGFR-TK which also had resemblance binding pattern to erlotinib with extra binding mode with Cys-773 at the gatekeeper of the enzyme. Cell c...
A new 2-thioquinazolinones series was designed and synthesized as HSP90 inhibitors based on the s... more A new 2-thioquinazolinones series was designed and synthesized as HSP90 inhibitors based on the structure of hit compound VII obtained by virtual screening approach. Their in vitro anti-proliferative activity was evaluated against three human cancer cell lines rich in HSP90 namely; colorectal carcinoma (HCT-116), and cervical carcinoma (Hela), breast carcinoma (MCF-7). Compounds 5a, 5d, 5e and 9h showed a significant broad spectrum anti-proliferative activity against all tested cell lines. They were characterized by potent effect against breast cancer in particular with IC50 of 11.73, 8.56, 7.35 and 9.48 μM, respectively against Doxorubicin (IC50 4.17 μM). HSP90 ATPase activity inhibition assay were conducted where compound 5d exhibited the best IC50 with 1.58 μM compared to Tanespimycin (IC50 = 2.17 μM). Compounds 5a and 9h showed higher IC50 values of 3.21 and 3.41 μM, respectively. The effects of 5a, 5d and 9h on Her2 (a client proteins of HSP90) and HSP70 were evaluated in MCF-7 cells. All tested compounds were found to reduce Her2 protein expression levels and induce Hsp70 protein expression levels significantly, emphasizing that antibreast cancer effect is a consequence of HSP90 chaperone inhibition. Cell cycle analysis of MCF-7 cells treated with 5d showed cell cycle arrest at G2/M phase 38.89% and pro-apoptotic activity as indicated by annexin V-FITC staining by 22.42%. Molecular docking studies suggested mode of interaction to HSP90 via hydrogen bonding. ADME properties prediction of the active compounds suggested that they could be used as orally absorbed anticancer drug candidates.
A series of new benzimidazole derivatives, namely 2-acylbenzimidazoles 2–9, a dihydroquinoxaline ... more A series of new benzimidazole derivatives, namely 2-acylbenzimidazoles 2–9, a dihydroquinoxaline 10, a benzoxazine 11, quinolines 13–15 and fused 1,2,4-triazines 17–24 were synthesized. Structure elucidation of the compounds was conducted using IR, 1H NMR, 13C NMR, mass spectral data and elemental analysis. These products were evaluated for in vitro antitumor activity against MCF7 cell line (human breast cancer). Compounds 13–15 and 24 manifested significant antitumor activity.
A series of new benzimidazole derivatives, namely 2-acylbenzimidazoles 2–9, a dihydroquinoxaline ... more A series of new benzimidazole derivatives, namely 2-acylbenzimidazoles 2–9, a dihydroquinoxaline 10, a benzoxazine 11, quinolines 13–15 and fused 1,2,4-triazines 17–24 were synthesized. Structure elucidation of the compounds was conducted using IR, 1H NMR, 13C NMR, mass spectral data and elemental analysis. These products were evaluated for in vitro antitumor activity against MCF7 cell line (human breast cancer). Compounds 13–15 and 24 manifested significant antitumor activity.
Design and synthesis of 2- phenyl benzimidazole derivatives as VEGFR- 2 inhibitors with anti- breast cancer activity , 2018
Three new series of 2- phenyl benzimidazole- based derivatives were designed, synthesized, and ev... more Three new series of 2- phenyl benzimidazole- based derivatives were designed, synthesized, and evaluated for their in vitro cytotoxic activity against breast cancer (MCF- 7) cell lines. Three compounds 8, 9, and 15 showed high cytotoxic activities, with IC50 values of 3.37, 6.30, and 5.84 μM, respectively, while they showed comparable cytotoxicity to the standard drug doxorubicin against human normal cells, including nontumorigenic breast epithelial cell line (MCF- 10F), skin fibroblast cell line (BJ), and lung fibroblast cell line (MRC- 5). Six of the synthesized compounds were screened against vascular endothelial growth factor receptor 2 (VEGFR- 2) where compounds 8, 9, 12, and 15 exhibited an outstanding potency in comparison with sorafenib, with IC50 values of 6.7–8.9 nM. Molecular docking study assessed the good binding patterns of the most potent compounds with the reported conserved amino acids of VEGFR- 2 active site.
Synthesis of new heterocyclic compounds containing benzimidazole moiety as inhibitors of breast cancer cell growth , 2013
A series of new benzimidazole derivatives, namely 2-acylbenzimidazoles 2– 9 , a dihydroquinoxa... more A series of new benzimidazole derivatives, namely 2-acylbenzimidazoles 2– 9 , a dihydroquinoxaline 10 , a benzoxazine 11 , quinolines 13– 1 5 and fused 1,2,4-triazines 17 – 24 were synthesized. Structure elucidation of the compounds was conducted using IR, 1 H NMR, 13 C NMR, mass spectral data and elemental analysis. These products were evaluated for in vitro antitumor activity against MCF7 cell line (human breast cancer). Compounds 13– 1 5 and 24 manifested significant antitumor activity. Certain quinolines [1 7– 2 0] and 1,2,4-triazines [2 1– 2 3] are also active. Hence, the aim of the current study was the synthesis of novel benzimidazole derivatives that incorporate benzoxazine, quinoxaline, quinoline and 1,2,4-triazine moieties. It was reasoned that this type of molecular combination might lead to finding compounds with improved antitumor activity.
New compounds of 4-anilino-6-substituted quinazoline were designed, synthesized and tested for th... more New compounds of 4-anilino-6-substituted quinazoline were designed, synthesized and tested for their EGFR-TK and tumor growth inhibitory activities. The synthesized compounds were appended with amides 6 and 7, dithiocarbamate ester 8a–f or urea/thiourea 9–12 moieties at C-6 of the quinazoline ring to work as extra hydrogen bond acceptors. All the synthesized compounds were effective against EGFR-TK activity, particularly, derivatives 8a, 8f and 9 with IC50 values of 0.14±0.003, 0.119±0.003, and 0.115±0.002 μM, respectively, showed the best activities. The three compounds were further assayed for their cytotoxicity against MCF-7, H-69, SKOV-3 and LS-174T cell lines. Multikinase enzymes inhibition activity of compound 9 was further screened including VEGFR-2, c-MER, c-MET and Her-2. Compounds 8a, 8f, and 9 were docked into the ATP binding site of EGFR-TK which also had resemblance binding pattern to erlotinib with extra binding mode with Cys-773 at the gatekeeper of the enzyme. Cell c...
A new 2-thioquinazolinones series was designed and synthesized as HSP90 inhibitors based on the s... more A new 2-thioquinazolinones series was designed and synthesized as HSP90 inhibitors based on the structure of hit compound VII obtained by virtual screening approach. Their in vitro anti-proliferative activity was evaluated against three human cancer cell lines rich in HSP90 namely; colorectal carcinoma (HCT-116), and cervical carcinoma (Hela), breast carcinoma (MCF-7). Compounds 5a, 5d, 5e and 9h showed a significant broad spectrum anti-proliferative activity against all tested cell lines. They were characterized by potent effect against breast cancer in particular with IC50 of 11.73, 8.56, 7.35 and 9.48 μM, respectively against Doxorubicin (IC50 4.17 μM). HSP90 ATPase activity inhibition assay were conducted where compound 5d exhibited the best IC50 with 1.58 μM compared to Tanespimycin (IC50 = 2.17 μM). Compounds 5a and 9h showed higher IC50 values of 3.21 and 3.41 μM, respectively. The effects of 5a, 5d and 9h on Her2 (a client proteins of HSP90) and HSP70 were evaluated in MCF-7 cells. All tested compounds were found to reduce Her2 protein expression levels and induce Hsp70 protein expression levels significantly, emphasizing that antibreast cancer effect is a consequence of HSP90 chaperone inhibition. Cell cycle analysis of MCF-7 cells treated with 5d showed cell cycle arrest at G2/M phase 38.89% and pro-apoptotic activity as indicated by annexin V-FITC staining by 22.42%. Molecular docking studies suggested mode of interaction to HSP90 via hydrogen bonding. ADME properties prediction of the active compounds suggested that they could be used as orally absorbed anticancer drug candidates.
A series of new benzimidazole derivatives, namely 2-acylbenzimidazoles 2–9, a dihydroquinoxaline ... more A series of new benzimidazole derivatives, namely 2-acylbenzimidazoles 2–9, a dihydroquinoxaline 10, a benzoxazine 11, quinolines 13–15 and fused 1,2,4-triazines 17–24 were synthesized. Structure elucidation of the compounds was conducted using IR, 1H NMR, 13C NMR, mass spectral data and elemental analysis. These products were evaluated for in vitro antitumor activity against MCF7 cell line (human breast cancer). Compounds 13–15 and 24 manifested significant antitumor activity.
A series of new benzimidazole derivatives, namely 2-acylbenzimidazoles 2–9, a dihydroquinoxaline ... more A series of new benzimidazole derivatives, namely 2-acylbenzimidazoles 2–9, a dihydroquinoxaline 10, a benzoxazine 11, quinolines 13–15 and fused 1,2,4-triazines 17–24 were synthesized. Structure elucidation of the compounds was conducted using IR, 1H NMR, 13C NMR, mass spectral data and elemental analysis. These products were evaluated for in vitro antitumor activity against MCF7 cell line (human breast cancer). Compounds 13–15 and 24 manifested significant antitumor activity.
Design and synthesis of 2- phenyl benzimidazole derivatives as VEGFR- 2 inhibitors with anti- breast cancer activity , 2018
Three new series of 2- phenyl benzimidazole- based derivatives were designed, synthesized, and ev... more Three new series of 2- phenyl benzimidazole- based derivatives were designed, synthesized, and evaluated for their in vitro cytotoxic activity against breast cancer (MCF- 7) cell lines. Three compounds 8, 9, and 15 showed high cytotoxic activities, with IC50 values of 3.37, 6.30, and 5.84 μM, respectively, while they showed comparable cytotoxicity to the standard drug doxorubicin against human normal cells, including nontumorigenic breast epithelial cell line (MCF- 10F), skin fibroblast cell line (BJ), and lung fibroblast cell line (MRC- 5). Six of the synthesized compounds were screened against vascular endothelial growth factor receptor 2 (VEGFR- 2) where compounds 8, 9, 12, and 15 exhibited an outstanding potency in comparison with sorafenib, with IC50 values of 6.7–8.9 nM. Molecular docking study assessed the good binding patterns of the most potent compounds with the reported conserved amino acids of VEGFR- 2 active site.
Synthesis of new heterocyclic compounds containing benzimidazole moiety as inhibitors of breast cancer cell growth , 2013
A series of new benzimidazole derivatives, namely 2-acylbenzimidazoles 2– 9 , a dihydroquinoxa... more A series of new benzimidazole derivatives, namely 2-acylbenzimidazoles 2– 9 , a dihydroquinoxaline 10 , a benzoxazine 11 , quinolines 13– 1 5 and fused 1,2,4-triazines 17 – 24 were synthesized. Structure elucidation of the compounds was conducted using IR, 1 H NMR, 13 C NMR, mass spectral data and elemental analysis. These products were evaluated for in vitro antitumor activity against MCF7 cell line (human breast cancer). Compounds 13– 1 5 and 24 manifested significant antitumor activity. Certain quinolines [1 7– 2 0] and 1,2,4-triazines [2 1– 2 3] are also active. Hence, the aim of the current study was the synthesis of novel benzimidazole derivatives that incorporate benzoxazine, quinoxaline, quinoline and 1,2,4-triazine moieties. It was reasoned that this type of molecular combination might lead to finding compounds with improved antitumor activity.
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Papers by Rania Gomaa
Certain quinolines [1 7– 2 0] and 1,2,4-triazines [2 1– 2 3] are also active. Hence, the aim of the current study was the synthesis of novel benzimidazole derivatives that incorporate benzoxazine, quinoxaline, quinoline and 1,2,4-triazine moieties. It was reasoned that this type of molecular combination might lead to finding compounds with improved antitumor activity.
Certain quinolines [1 7– 2 0] and 1,2,4-triazines [2 1– 2 3] are also active. Hence, the aim of the current study was the synthesis of novel benzimidazole derivatives that incorporate benzoxazine, quinoxaline, quinoline and 1,2,4-triazine moieties. It was reasoned that this type of molecular combination might lead to finding compounds with improved antitumor activity.