Synthesis and biological evaluation of novel 5-chloro-N-(4-sulfamoylbenzyl) salicylamide derivatives as tubulin polymerization inhibitors. Issue 9 (10th August 2018)

• Record Type: Journal Article
• Authors: Galal, Alaaeldin M. F.; Soltan, Maha M.; Ahmed, Esam R.; Hanna, Atef G.
• Is Part Of: MedChemComm. Volume 9:Issue 9(2018)
• Page Start: 1511
• Page End: 1528
• Publication Date: 2018-08-10
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19
• DOI: 10.1039/c8md00214b
• Languages: English
• ISSNs: 2040-2503

Abstract

Abstract : A novel series of sulfonamide derivatives, coupled with a salicylamide scaffold, was designed and synthesized. Abstract : A novel series of sulfonamide derivatives, coupled with a salicylamide scaffold, was designed and synthesized. The structures of the synthesized compounds were established using 1 H NMR, 13 C NMR and high-resolution mass spectroscopy. The synthesized compounds were tested in vitro against five types of human cell lines. Two were breast adenocarcinoma, including the hormone-dependent MCF-7 and the hormone-independent MDA-MB-231. The others were the colorectal adenocarcinoma Caco-2, the carcinoma HCT-116 and the immortalized retinal-pigmented epithelium, hTERT-RPE1. Nine sulfonamides were able to inhibit the growth of the four tested cancer cells. Compound33 was the most active against the selected colon cancer (Caco-2 and HCT-116) subtypes, while compound24 showed the best efficacy against the examined breast cancer (MCF-7 and MDA-MB-231) cells. The selectivity index introduced compounds24 and33 as having the best selectivity among the breast and colon subtypes, respectively. In vitro tubulin polymerization experiments and flow cytometric assays showed that compounds24 and33 led to cell cycle arrest at the G2/M phase in a dose-dependent manner by effectively inhibiting tubulin polymerization. Furthermore, the results of the molecular docking studies indicate that this class of compounds can bind to the colchicine-binding site of tubulin.