Design, synthesis of anticancer and anti-inflammatory 4-(1-methyl-1H-indol-3-yl)-6-(methylthio) pyrimidine-5-carbonitriles

A novel series of 4-(1-methyl-1H-indol-3-yl)-6-(methylthio) pyrimidine-5-carbonitriles (4a–i) was synthesized and evaluated for anticancer potential against cell lines for breast cancer. Compounds 4b, 4e, and 4h exhibited prominent cytotoxicity against human breast carcinoma MCF-7 cell line with GI50 of 2.0, 0.5, and 0.5 µM, respectively. Molecular docking study against EGFR tyrosine kinase could provide valuable insights into the plausible mechanism of action. The compounds could bind with significantly high binding affinity and their binding affinity scores could correlate well with the observed anticancer activity. Furthermore, compounds 4a, 4c, 4e, 4g, and 4i exhibited significant inflammatory activities as well which could expand the therapeutic domain of this novel series.