Synthesis and Anticancer Evaluation of Novel Indole Based Arylsulfonylhydrazides against Human Breast Cancer Cells

Abstract

A series of novel indole based sulfonohydrazide derivatives (<b>5a</b>-<b>k</b>) containing morpholine heterocyclic ring were synthesized through multistep chemical reactions. The target compounds (<b>5a</b>-<b>k</b>) were prepared by the reaction of substituted phenyl sulfonylhydrazides (<b>2a</b>-<b>k</b>) with morpholine derivative of indole 3-carboxaldehyde. All the target compounds were screened for their anticancer activity <i>in vitro</i> against the estrogen receptor-positive breast cancer line MCF-7 and triple-negative breast cancer cell line, MDA-MB-468. It was found that among all the evaluated compounds, the chemotype 4-chloro-<i>N</i>'-((1-(2-morpholinoethyl)-1<i>H</i>-indol-3-yl)methylene)benzenesulfonohydrazide (<b>5f</b>) showed promising inhibition of both MCF-7 and MDA-MB-468 cancer cells with the respective IC₅₀ values of 13.2 μM and 8.2 μM. Compound <b>5f</b> was found to be nontoxic against HEK 293 noncancerous cells in the studied concentration range, therefore indicating that such chemotypes inhibit the proliferation of cancerous cells selectively and significantly.