Synthesis and biological evaluation of novel Δ2-isoxazoline fused cyclopentane derivatives as potential antimicrobial and anticancer agents

MedChemComm
2015.0

Abstract

As a part of our endeavour toward the synthesis of new heterocyclic bioactive agents, three series of ∆2 -isoxazoline fused cyclopentane derivatives (27 compounds) were synthesized and characterized by IR, 1H NMR, 13C NMR and MS analysis. The newly synthesized target compounds were evaluated for their preliminary in vitro antimicrobial and anticancer activities. The results indicated that the compounds 4b, 4h, 4i, 5d and 5g displayed remarkable anti-microbial activity with respect to their standard drugs Ampicillin, Gentamycin and Amphotericin B. In preliminary MTT cytotoxicity studies, compound 4i was found to be equipotent to the standard drug Etoposide against MCF-7. The influence of the most active cytotoxic compound 4i, on the cell cycle distribution was evaluated in the MCF-7 cell line, which displayed a cell cycle arrest at S phase. Moreover, Acridine orange/ethidium bromide staining, annexin V binding assay and mitochondrial membrane potential revealed that the compound 4i can induce cell apoptosis in MCF-7 cells. Compounds 4b and 4h are potential leads as antimicrobials owing to no significant cell toxicity observed in present study. Docking studies revealed that compound 4i binds to Phe1145, Glh698, Met696, Cys1191, Met1169 and Ile1167 on DNA methyltransferase (DNMT1) protein and inhibition of DNMT1 could be the possible mechanism of action for these compounds.

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