Issue 5, 2015

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.

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

Supplementary files

Article information

Article type
Concise Article
Submitted
18 Nov 2014
Accepted
11 Feb 2015
First published
11 Feb 2015

Med. Chem. Commun., 2015,6, 839-845

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

S. K. Prajapti, S. Shrivastava, U. Bihade, A. K. Gupta, V. G. M. Naidu, U. C. Banerjee and B. N. Babu, Med. Chem. Commun., 2015, 6, 839 DOI: 10.1039/C4MD00525B

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Spotlight

Advertisements