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

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 IC501.18 mu M, 5.28 mu M and 7.15 mu M against MCF-7, Caco2 and HepG-2, respectively. Moreover, the dihydroxyphenyl triazene derivative 5 demonstrated IC503.03 mu M, 5.66 mu M and 12.50 mu M against Caco2, HepG-2 and MCF-7, respec- tively. Similarly, the carbohydrazide coumarin 18 showed IC50 of 2.00 mu M and 12.30 mu M 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.(c) 2023 The Author(s). Published by Elsevier B.V. on behalf of King Saud University.This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Automated summary

New thiadiazole sulfonamide derivatives were designed as human carbonic anhydrase inhibitors (hCAIs) to develop robust and novel anticancer agents. The target compounds were synthesized using a two-step procedure starting from 5-acetyl-3-N-(4-sulfamoylphenyl)-2-imino-1,3,4-thiadiazoline and a tail modification approach. Cytotoxic evaluation revealed the potent activity of the synthesized compounds against various cancer cell lines, and molecular docking and ADME evaluation provided insights into their mechanism of action.