Abstract
In the present work, 12 novel Schiff’s bases containing a thiadiazole scaffold and benzamide groups coupled through appropriate pharmacophore were synthesized. These moieties are associated with important biological properties. A facile, solvent-free synthesis of a series of novel 7(a–l) N-((5-(substituted methylene amino)-1,3,4-thiadiazol-2-yl)methyl) benzamide was carried out under microwave irradiation. Structures of the synthesized compounds were confirmed by IR, NMR, mass spectral study and elemental analysis. All the synthesized hybrids were evaluated for their in vitro anticancer activity against a panel of four human cancer cell lines, viz. SK-MEL-2 (melanoma), HL-60 (leukemia), HeLa (cervical cancer), MCF-7 (breast cancer) and normal breast epithelial cell (MCF-10A) using 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay method. Most of the synthesized compounds exhibited promising anticancer activity, showed comparable GI50 values comparable to that of the standard drug Adriamycin. The compounds 7k, 7l, 7b, and 7a were found to be the most promising anticancer agents in this study. A molecular docking study was performed to predict the probable mechanism of action and computational study of the synthesized compounds 7(a–l) was performed to predict absorption, distribution, metabolism, excretion and toxicity (ADMET) properties, by using QikProp v3.5 (Schrödinger LLC). The results showed the good oral drug-like behavior of the synthesized compounds 7(a–l).
Highlights
Cancer is a disease in which cells grow and proliferate in an uncontrolled manner
The N-((5(substituted methylene amino)-1,3,4-thiadiazol-2-yl)methyl) benzamide derivatives were synthesized from N-((5-amino-1,3,4-thiadiazol-2-yl)methyl)
The results indicated that the compounds 7k, 7l, 7a and 7b exhibited significant cancer cell growth inhibition compared to reference standard Adriamycin against MCF-7, HeLa, SKMEL-2 and HL-60 cancer cell lines
Summary
Cancer is a disease in which cells grow and proliferate in an uncontrolled manner. Cancer evokes a high level of mortality regardless of the recent advances in the development of clinically authorized anticancer agents [1,2,3].The development of resistance to chemotherapeutic agents and associated side effects are major obstacles to effectively treating cancer [3]. Cancer is a disease in which cells grow and proliferate in an uncontrolled manner. Cancer evokes a high level of mortality regardless of the recent advances in the development of clinically authorized anticancer agents [1,2,3]. The development of resistance to chemotherapeutic agents and associated side effects are major obstacles to effectively treating cancer [3]. It is necessary to identify and develop new anticancer agents with improved efficacy and reduced side effects to complement the present chemotherapeutic. Further research towards the development of newer therapeutic drugs that more effectively combat cancer is needed. One of the potential targets for new drugs is the matrix metalloproteinases (MMPs), a group of proteinases that have physiologic roles in degrading and remodeling the extracellular membrane
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