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

Abstract

As a part of our endeavour toward the synthesis of new heterocyclic bioactive agents, three series of Δ²-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 vitroantimicrobial and anticancer activities. The results indicated that compounds 4b, 4h, 4i, 5d and 5g displayed remarkable anti-microbial activity with respect to their standard drugsAmpicillin, Gentamycin and Amphotericin B. In preliminary MTT cytotoxicity studies, compound 4i was found to be equipotent to the standard drugEtoposide 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 the S phase. Moreover, acridine orange/ethidium bromide staining, annexin V binding assay and mitochondrial membrane potential revealed that 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 the 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.