One-pot synthesis and anticancer studies of 2-arylamino-5-aryl-1,3,4-thiadiazoles

Abstract

A series of 2-arylamino-5-aryl-1,3,4-thiadiazoles 1a–j were synthesized and screened for their anticancer activity against various human cancer cell lines. The novel one-pot synthesis of 1,3,4-thiadiazoles was achieved by refluxing aryl aldehydes, hydrazine hydrate, and aryl isothiocyanates in methanol followed by oxidative cyclization with ferric ammonium sulfate. The compounds 1g–j with trimethoxyphenyl at the C-5 position displayed extremely potent anticancer activity with at least twofold selectivity (IC50: 4.3–9.2 μM). The nature of substituent on the C-2 arylamino ring may be critical in opting for the selectivity towards a particular cancer cell.