A series of nineteen (1-19) indole-based-thiadiazole derivatives were synthesized, characterized ... more A series of nineteen (1-19) indole-based-thiadiazole derivatives were synthesized, characterized by 1HNMR, 13C NMR, MS, and screened for α-glucosidase inhibition. All analogs showed varied α-glucosidase inhibitory potential with IC50 value ranged between 0.95 ± 0.05 to 13.60 ± 0.30 µM, when compared with the standard acarbose (IC50 = 1.70 ± 0.10). Analogs 17, 2, 1, 9, 7, 3, 15, 10, 16, and 14 with IC50 values 0.95 ± 0.05, 1.10 ± 0.10, 1.30 ± 0.10, 1.60 ± 0.10, 2.30 ± 0.10, 2.30 ± 0.10, 2.80 ± 0.10, 4.10 ± 0.20 and 4.80 ± 0.20 µM respectively showed highest α-glucosidase inhibition. All other analogs also exhibit excellent inhibitory potential. Structure activity relationships have been established for all compounds primarily based on substitution pattern on the phenyl ring. Through molecular docking study, binding interactions of the most active compounds were confirmed. We further studied the kinetics study of analogs 1, 2, 9 and 17 and found that they are Non-competitive inhibitors.
Abstract The last decade has witnessed an extensive use of biodegradable and biocompatible polyme... more Abstract The last decade has witnessed an extensive use of biodegradable and biocompatible polymers for biomedical applications. Concerning drug delivery the use of such polymers is of high importance among other types of polymers. The encapsulation of active molecules within a polymeric nanostructure yields many benefits such as enhanced drug bioavailability, sustained drug release, heightened drug efficiency, and a better control of drug targeting that by its turn are able to reduce the toxicity and side effects of the encapsulated molecule. In addition, encapsulation can protect the drug from natural barriers after administration, which permits a better control of the disease. In this work the preparation of polymeric nanocontainers was discussed, from the preparation methods used to their applications. Moreover, several methods for tweaking the particles were highlighted, the targeting strategies of the drug, and the effect of particles on the biodistribution was examined.
Breast cancer treatment mostly revolved around radiation therapy and surgical interventions, thes... more Breast cancer treatment mostly revolved around radiation therapy and surgical interventions, these treatments doesn’t provide satisfactory relief to the patients and carry unmanageable side-effects. Nanomaterials show promising results in treating cancer cells and have many advantages such as high biocompatibility, bioavailability and effective therapeutic capabilities. Interestingly, fluorescent magnetic nanoparticles have been used in many biological and diagnostic applications, but there is no report of use of fluorescent magnetic submicronic polymer nanoparticles (FMSP-nanoparticles) in the treatment of human breast cancer cells. In the present study, we have tested the effect FMSP-nanoparticles on human breast cancer cells (MCF-7). We have tested different concentrations (1.25µg/1mL, 12.5µg/mL and 50µg/1mL) of FMSP-nanoparticles in MCF-7 cells and evaluated the nanoparticles response morphometrically. Our results revealed that FMSP-nanoparticles produced...
Abstract Triple combination FCR (fludarabine, cyclophosphamide and rituximab) is often used as fr... more Abstract Triple combination FCR (fludarabine, cyclophosphamide and rituximab) is often used as front-line treatment for chronic lymphocytic leukemia (CLL) and non-Hodgkin’s lymphoma. Results from our laboratory indicate that 2-FaraAMP (fludarabine) has multiple mechanisms of cytotoxicity that include accumulation of isoforms and phosphorylated derivatives of p53, and induction of the unfolded protein response (UPR). Using protein pull-downs with Dynabeads coated with p53 antibody, we have found that 2-FaraA (fludarabine nucleoside) induces major changes in the p53 interactome in human Raji lymphoma and IM9 multiple myeloma cells. These changes are likely driven by DNA strand breaks induced by 2-FaraA that activate protein kinases such as ATM, ATR and Chk1.
Abstract In mammals, AMPylation of cellular proteins is carried out by Huntingtin yeast-interacti... more Abstract In mammals, AMPylation of cellular proteins is carried out by Huntingtin yeast-interacting protein E, and pseudokinase SelO. Lysates from mouse B16-F10 melanoma cells have been fractionated by immuno-precipitation using magnetic Dynabeads coated with antibodies against both adenosine 5′-monophosphate in phosphate ester linkage to tyrosine, and adenosine-phosphate. Proteins pulled down with both these antibodies were subject to post-translational modification, most likely AMPylation. Using tandem mass spectrometry, analysis of these protein fractions identified 333 proteins that could be pulled down by both antibodies. Many of these proteins clustered in 13 functional Ingenuity Pathway Analysis categories of 4 or more adenylated proteins including some from the cytoskeleton, and some involved with initiating the unfolded protein response. Supplemental data for this article is available online at https://doi.org/10.1080/15257770.2021.1995608 .
Both nanoparticles and cloves (Syzygium aromaticum) possess anticancer properties, but they do no... more Both nanoparticles and cloves (Syzygium aromaticum) possess anticancer properties, but they do not elicit a significant response on cancer cells when treated alone. In the present study, we have tested fluorescent magnetic submicronic polymer nanoparticles (FMSP-nanoparticles) in combination with crude clove extracts on human breast cancer cells (MCF-7) to examine whether the combination approach enhance the cancer cell death. The MCF-7 cells were treated with different concentrations (1.25 μg/mL, 12.5 μg/mL, 50 μg/mL, 75 μg/mL, and 100 μg/mL) of FMSP-nanoparticles alone and in combination with 50 μg/mL crude clove extracts. The effects of FMSP-nanoparticles alone and combined with clove extracts were observed after 24 hrs and 48 hrs intervals. The response of FMSP-nanoparticles-treated cells was evaluated by Trypan Blue, 4′,6-diamidino-2-phenylindole (DAPI), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, respectively. We have demonstrated that cancer...
High-grade serous ovarian cancer (HGSOC) is the most lethal gynecological malignancy among women.... more High-grade serous ovarian cancer (HGSOC) is the most lethal gynecological malignancy among women. Several obstacles impede the early diagnosis and effective treatment options for ovarian cancer (OC) patients, which most importantly include the development of platinum-drug-resistant strains. Currently, extensive efforts are being put into the development of strategies capable of effectively circumventing the physical and biological barriers present in the peritoneal cavity of metastatic OC patients, representing a late stage of gastrointestinal and gynecological cancer with an extremely poor prognosis. Naturally occurring extracellular vesicles (EVs) have been shown to play a pivotal role in progression of OC and are now being harnessed as a delivery vehicle for cancer chemotherapeutics. However, there are limitations to their clinical application due to current challenges in their preparation techniques. Intriguingly, there is a recent drive towards the use of engineered synthetic E...
Polymer nanoparticles are a promising approach for cancer treatment and detection, due to their b... more Polymer nanoparticles are a promising approach for cancer treatment and detection, due to their biocompatibility, biodegradability, targeting capabilities, capacity for drug loading and long blood circulation time. This study aims to evaluate the impact of poly (styrene–acrylic acid) latex particles on colorectal and cervical cancer cells for anti-tumor efficiency. Latex particles were synthesized by a surfactant-free radical emulsion polymerization process and the obtained polymer particles were characterized in terms of size, size distribution, morphology using scanning electron microscopy (SEM) and transmission electron microscopy (TEM), and electrokinetic property (i.e., zeta potential). Human colorectal and cervical cancer, and normal cell lines, were then treated with different concentrations of poly (styrene–acrylic acid) latex particles. The cell morphology changes were pointed out using an optical microscope and the nanoparticles’ (NPs) cell cytotoxicity was evaluated using...
Abstract Each year a large number of people lose their lives because of well-studied diseases suc... more Abstract Each year a large number of people lose their lives because of well-studied diseases such as diabetes mellitus, cancer, and neurodegenerative and cardiovascular diseases. Cancer is one of these diseases and drugs used for its treatment have a high toxicity. The nonspecific delivery of these toxic drugs to different parts of the body through dosage forms is an immense challenge within the treatment of numerous diseases. However, there are several opportunities that have been created through biomedical nanotechnology for diagnosis of, and therapies for, health problems. In fact, advanced drug delivery development has attracted a special attention to deliver drugs to the suitable organ and tissue. Indeed, nanotechnology can be taken into account as one of the useful approaches for the diagnosis, treatment, and prevention of cancer disease. Thanks to the imaging characteristics and therapeutic properties of magnetic metal oxide nanoparticles as Fe3O4 and γ-Fe2O3 maghemite, they took an outstanding place for biomedical applications among other different nanoparticles. Through the application of a magnetic field, magnetic nanoparticles (MNPs) can easily enter into the lesion area due to their small size and large specific area. Furthermore, magnetic nanoparticle properties are appealing, including surface charge nature and density, shape, chemical composition, size, degradation, internal morphology, and responsiveness to stimuli of pH, light, and temperature. At the present time, a new subfield named theranostics came out due to MNPs’ double function in diagnosis and therapy. Thus MNPs attract significant attention in the treatment of diseases, especially for cancer. This chapter is focused on some of the newest developments concerning MNPs.
A series of nineteen (1-19) indole-based-thiadiazole derivatives were synthesized, characterized ... more A series of nineteen (1-19) indole-based-thiadiazole derivatives were synthesized, characterized by 1HNMR, 13C NMR, MS, and screened for α-glucosidase inhibition. All analogs showed varied α-glucosidase inhibitory potential with IC50 value ranged between 0.95 ± 0.05 to 13.60 ± 0.30 µM, when compared with the standard acarbose (IC50 = 1.70 ± 0.10). Analogs 17, 2, 1, 9, 7, 3, 15, 10, 16, and 14 with IC50 values 0.95 ± 0.05, 1.10 ± 0.10, 1.30 ± 0.10, 1.60 ± 0.10, 2.30 ± 0.10, 2.30 ± 0.10, 2.80 ± 0.10, 4.10 ± 0.20 and 4.80 ± 0.20 µM respectively showed highest α-glucosidase inhibition. All other analogs also exhibit excellent inhibitory potential. Structure activity relationships have been established for all compounds primarily based on substitution pattern on the phenyl ring. Through molecular docking study, binding interactions of the most active compounds were confirmed. We further studied the kinetics study of analogs 1, 2, 9 and 17 and found that they are Non-competitive inhibitors.
Abstract The last decade has witnessed an extensive use of biodegradable and biocompatible polyme... more Abstract The last decade has witnessed an extensive use of biodegradable and biocompatible polymers for biomedical applications. Concerning drug delivery the use of such polymers is of high importance among other types of polymers. The encapsulation of active molecules within a polymeric nanostructure yields many benefits such as enhanced drug bioavailability, sustained drug release, heightened drug efficiency, and a better control of drug targeting that by its turn are able to reduce the toxicity and side effects of the encapsulated molecule. In addition, encapsulation can protect the drug from natural barriers after administration, which permits a better control of the disease. In this work the preparation of polymeric nanocontainers was discussed, from the preparation methods used to their applications. Moreover, several methods for tweaking the particles were highlighted, the targeting strategies of the drug, and the effect of particles on the biodistribution was examined.
Breast cancer treatment mostly revolved around radiation therapy and surgical interventions, thes... more Breast cancer treatment mostly revolved around radiation therapy and surgical interventions, these treatments doesn’t provide satisfactory relief to the patients and carry unmanageable side-effects. Nanomaterials show promising results in treating cancer cells and have many advantages such as high biocompatibility, bioavailability and effective therapeutic capabilities. Interestingly, fluorescent magnetic nanoparticles have been used in many biological and diagnostic applications, but there is no report of use of fluorescent magnetic submicronic polymer nanoparticles (FMSP-nanoparticles) in the treatment of human breast cancer cells. In the present study, we have tested the effect FMSP-nanoparticles on human breast cancer cells (MCF-7). We have tested different concentrations (1.25µg/1mL, 12.5µg/mL and 50µg/1mL) of FMSP-nanoparticles in MCF-7 cells and evaluated the nanoparticles response morphometrically. Our results revealed that FMSP-nanoparticles produced...
Abstract Triple combination FCR (fludarabine, cyclophosphamide and rituximab) is often used as fr... more Abstract Triple combination FCR (fludarabine, cyclophosphamide and rituximab) is often used as front-line treatment for chronic lymphocytic leukemia (CLL) and non-Hodgkin’s lymphoma. Results from our laboratory indicate that 2-FaraAMP (fludarabine) has multiple mechanisms of cytotoxicity that include accumulation of isoforms and phosphorylated derivatives of p53, and induction of the unfolded protein response (UPR). Using protein pull-downs with Dynabeads coated with p53 antibody, we have found that 2-FaraA (fludarabine nucleoside) induces major changes in the p53 interactome in human Raji lymphoma and IM9 multiple myeloma cells. These changes are likely driven by DNA strand breaks induced by 2-FaraA that activate protein kinases such as ATM, ATR and Chk1.
Abstract In mammals, AMPylation of cellular proteins is carried out by Huntingtin yeast-interacti... more Abstract In mammals, AMPylation of cellular proteins is carried out by Huntingtin yeast-interacting protein E, and pseudokinase SelO. Lysates from mouse B16-F10 melanoma cells have been fractionated by immuno-precipitation using magnetic Dynabeads coated with antibodies against both adenosine 5′-monophosphate in phosphate ester linkage to tyrosine, and adenosine-phosphate. Proteins pulled down with both these antibodies were subject to post-translational modification, most likely AMPylation. Using tandem mass spectrometry, analysis of these protein fractions identified 333 proteins that could be pulled down by both antibodies. Many of these proteins clustered in 13 functional Ingenuity Pathway Analysis categories of 4 or more adenylated proteins including some from the cytoskeleton, and some involved with initiating the unfolded protein response. Supplemental data for this article is available online at https://doi.org/10.1080/15257770.2021.1995608 .
Both nanoparticles and cloves (Syzygium aromaticum) possess anticancer properties, but they do no... more Both nanoparticles and cloves (Syzygium aromaticum) possess anticancer properties, but they do not elicit a significant response on cancer cells when treated alone. In the present study, we have tested fluorescent magnetic submicronic polymer nanoparticles (FMSP-nanoparticles) in combination with crude clove extracts on human breast cancer cells (MCF-7) to examine whether the combination approach enhance the cancer cell death. The MCF-7 cells were treated with different concentrations (1.25 μg/mL, 12.5 μg/mL, 50 μg/mL, 75 μg/mL, and 100 μg/mL) of FMSP-nanoparticles alone and in combination with 50 μg/mL crude clove extracts. The effects of FMSP-nanoparticles alone and combined with clove extracts were observed after 24 hrs and 48 hrs intervals. The response of FMSP-nanoparticles-treated cells was evaluated by Trypan Blue, 4′,6-diamidino-2-phenylindole (DAPI), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, respectively. We have demonstrated that cancer...
High-grade serous ovarian cancer (HGSOC) is the most lethal gynecological malignancy among women.... more High-grade serous ovarian cancer (HGSOC) is the most lethal gynecological malignancy among women. Several obstacles impede the early diagnosis and effective treatment options for ovarian cancer (OC) patients, which most importantly include the development of platinum-drug-resistant strains. Currently, extensive efforts are being put into the development of strategies capable of effectively circumventing the physical and biological barriers present in the peritoneal cavity of metastatic OC patients, representing a late stage of gastrointestinal and gynecological cancer with an extremely poor prognosis. Naturally occurring extracellular vesicles (EVs) have been shown to play a pivotal role in progression of OC and are now being harnessed as a delivery vehicle for cancer chemotherapeutics. However, there are limitations to their clinical application due to current challenges in their preparation techniques. Intriguingly, there is a recent drive towards the use of engineered synthetic E...
Polymer nanoparticles are a promising approach for cancer treatment and detection, due to their b... more Polymer nanoparticles are a promising approach for cancer treatment and detection, due to their biocompatibility, biodegradability, targeting capabilities, capacity for drug loading and long blood circulation time. This study aims to evaluate the impact of poly (styrene–acrylic acid) latex particles on colorectal and cervical cancer cells for anti-tumor efficiency. Latex particles were synthesized by a surfactant-free radical emulsion polymerization process and the obtained polymer particles were characterized in terms of size, size distribution, morphology using scanning electron microscopy (SEM) and transmission electron microscopy (TEM), and electrokinetic property (i.e., zeta potential). Human colorectal and cervical cancer, and normal cell lines, were then treated with different concentrations of poly (styrene–acrylic acid) latex particles. The cell morphology changes were pointed out using an optical microscope and the nanoparticles’ (NPs) cell cytotoxicity was evaluated using...
Abstract Each year a large number of people lose their lives because of well-studied diseases suc... more Abstract Each year a large number of people lose their lives because of well-studied diseases such as diabetes mellitus, cancer, and neurodegenerative and cardiovascular diseases. Cancer is one of these diseases and drugs used for its treatment have a high toxicity. The nonspecific delivery of these toxic drugs to different parts of the body through dosage forms is an immense challenge within the treatment of numerous diseases. However, there are several opportunities that have been created through biomedical nanotechnology for diagnosis of, and therapies for, health problems. In fact, advanced drug delivery development has attracted a special attention to deliver drugs to the suitable organ and tissue. Indeed, nanotechnology can be taken into account as one of the useful approaches for the diagnosis, treatment, and prevention of cancer disease. Thanks to the imaging characteristics and therapeutic properties of magnetic metal oxide nanoparticles as Fe3O4 and γ-Fe2O3 maghemite, they took an outstanding place for biomedical applications among other different nanoparticles. Through the application of a magnetic field, magnetic nanoparticles (MNPs) can easily enter into the lesion area due to their small size and large specific area. Furthermore, magnetic nanoparticle properties are appealing, including surface charge nature and density, shape, chemical composition, size, degradation, internal morphology, and responsiveness to stimuli of pH, light, and temperature. At the present time, a new subfield named theranostics came out due to MNPs’ double function in diagnosis and therapy. Thus MNPs attract significant attention in the treatment of diseases, especially for cancer. This chapter is focused on some of the newest developments concerning MNPs.
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