Synthesis of New Heteroaryl a-Aminophosphonates and Evaluation of Their Cytotoxicity against Human Breast Cancer MCF-7 Cell Lines

摘要

Breast cancer has a rate of occurrence of one in nine. Aromatase also named estrogen synthase which is found to be associated with breast cancer and it has also been one of the targets for treatment and the current work explores the potentiality of a new heteroaryl α-aminophosphonates 9a-j. The new heteroaryl α-aminophosphonates 9a-j were synthesized using the reactions involving 2-aminobenzothiazole (6), various heteroaryl aldehydes 7a-j and 2,3-dihydro[1,3,2]oxaza-phospholo[4,5-b]pyridine-2-oxide (5). The QSAR (quantitative structure activity relationship) descriptors, PreADMET (adsorption, distribution, metabolism, excretion and toxicity) analysis and binding interaction simulation studies with X-Ray crystallographic structure of Aromatase have positively forwarded us for the cytotoxicity evaluation of the title compounds by Morphological study, Cell proliferation inhibition assay (MTT), Lactate dehydrogenase (LDH) assay and Hoechst staining (apoptosis). An improved apoptotic cell number was observed in Hoechst staining using compounds 9e and 9h further corroborated by LDH assay. Current work supports to conclude the promising ability of the title compounds to induce apoptosis through nuclear fragmentation of breast cancer cells by regulating their metabolic functions.