Synthesis and Evaluation of Heterocycles Based Chalcone Derivatives as Antiproliferative Agents

Abstract

Background: The lack of selectivity and development of drug-resistance encourage researchers to search for novel, more efficient and multi-targeted agents with less toxicity.

Objective: In this paper, a series of novel chalcone derivatives bearing diverse heterocycles have been synthesized and evaluated for their antiproliferative activity against A549 (Human Lung Adenocarcinoma) and C6 (Rat Brain Glioma) cells.

Method: Structures of the title compounds (3-18) were verified by FT-IR, 1H NMR, 13C NMR, HRMS spectral data and elemental analyses. Antiproliferative activities of the compounds were evaluated using MTT assay, BrdU method, and flow cytometric analysis.

Results: Compounds 9 and 15 were revealed as the most promising cytotoxic agents due to their selectivity towards A549 cells with lower IC50 values (IC50=0.05 µM and IC50=0.0316 µM) than cisplatin (IC50=0.06 µM). Flow cytometric analysis of compounds 9 and 15 showed that they affected lung cancer cells by the apoptotic pathway.

Conclusion: It is concluded that this study will contribute to the research of novel antiproliferative agents.

Keywords: Chalcone; antiproliferative activity; apoptotic pathway; cytotoxicity; derivatives; heterocycles..