Issue 3, 2024

Synthesis, molecular docking analysis and in vitro evaluation of new heterocyclic hybrids of 4-aza-podophyllotoxin as potent cytotoxic agents

Abstract

Two different synthetic approaches to novel heterocyclic hybrid compounds of 4-azapodophyllotoxin were investigated. The obtained products were characterized by infrared spectroscopy, nuclear magnetic resonance spectroscopy, and high-resolution mass spectrometry. MTT protocol was then performed to examine the cytotoxic activity of these products against KB, HepG2, A549, MCF7, and Hek-293 cell lines. The cytotoxic assessment indicated that all products displayed moderate to high cytotoxicity against all tested cancer cell lines. The most active compound 13k containing the 2-methoxypyridin-4-yl group exhibited selective cytotoxicity against KB, A549, and HepG2 cell lines with the IC50 values ranging from 0.23 to 0.27 ÎĽM, which were between 5- to 10-fold more potent than the positive control ellipticine. Compounds 13a (HetAr = thiophen-3-yl) and 13d (HetAr = 5-bromofuran-2-yl) displayed high cytotoxic selectivity for A549 and HepG2 cancer cell lines when compared to the other cancer cell lines and low toxicity to the normal Hek-293 cell line. Molecular docking study was conducted to evaluate the interaction of new synthesized compounds with the colchicine-binding-site of tubulin. Besides that, physicochemical and pharmacokinetic properties of the most active compounds 13h,k were predicted.

Graphical abstract: Synthesis, molecular docking analysis and in vitro evaluation of new heterocyclic hybrids of 4-aza-podophyllotoxin as potent cytotoxic agents

Supplementary files

Article information

Article type
Paper
Submitted
30 Oct 2023
Accepted
27 Dec 2023
First published
08 Jan 2024
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2024,14, 1838-1853

Synthesis, molecular docking analysis and in vitro evaluation of new heterocyclic hybrids of 4-aza-podophyllotoxin as potent cytotoxic agents

H. T. Nguyen, K. T. Van, H. Pham-The, J. Braire, P. H. Thi, T. A. Nguyen, Q. G. Nguyen Thi, T. A. Dang Thi, G. Le-Nhat-Thuy, T. A. Le Thi, D. V. Ngoc and T. Nguyen Van, RSC Adv., 2024, 14, 1838 DOI: 10.1039/D3RA07396C

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