Design, synthesis, cytotoxic evaluation and molecular docking of novel 1, 3, 4-thiadiazole sulfonamides with azene and coumarin moieties as carbonic anhydrase inhibitors

Abstract

New thiadiazole sulfonamide derivatives were designed as human carbonic anhydrase inhibitors (hCAIs) to develop robust and novel anticancer agents. Tail modification approach was considered in designing the target compounds which were synthesized following the two-step procedure starting from 5-acetyl-3-N-(4-sulfamoylphenyl)-2-imino-1,3,4-thiadiazoline. Cytotoxic evaluation revealed the potent diazene derivative 2 with IC50 1.18 μM, 5.28 μM and 7.15 μM against MCF-7, Caco2 and HepG-2, respectively. Moreover, the dihydroxyphenyl triazene derivative 5 demonstrated IC50 3.03 μM, 5.66 μM and 12.50 μM against Caco2, HepG-2 and MCF-7, respectively. Similarly, the carbohydrazide coumarin 18 showed IC50 of 2.00 μM and 12.30 μM against Caco2 and HepG2, respectively. Molecular docking using hCAIX and hCAXII were adopted to explain the achieved cytotoxicity on molecular level with their in silico ADME evaluation.