Synthesis and Biological Evaluation of Benzo[d] thiazolyl-Sulfonyl-Benzo[4,5]isothiazolo [2,3-c][1,2,3] triazole Derivatives as EGFR Targeting Anticancer Agents

A one-step procedure for the synthesis of new fused Benzo[d]thiazolo-1,2,3-triazoles (3 a-3 h and 4 a-4 h) in good yields using sulfonylazides (2) and iodoalkyne (1) through from the 5-iodo 1,2,3-triazole generated in situ was developed. Among all, compounds 5-chloro-3-(((1,1-dioxidobenzo[d]thiazol-2-yl)sulfonyl)methyl)benzo[4,5]isothiazolo[2,3-c] [1,2,3]triazole 8,8-dioxide (3 e), 3-(((1,1-dioxidobenzo[d]thiazol-2-yl)sulfonyl)methyl)-5-fluorobenzo[4,5]isothiazolo [2,3-c][1,2,3]triazole 8,8-dioxide (3 f), 5-bromo-3-(((5-bromo-1,1-dioxidobenzo[d]thiazol-2-yl)sulfonyl)methyl)benzo [4,5]isothiazolo[2,3-c][1,2,3]triazole 8,8-dioxide (4 d), 3-(((5-bromo-1,1-dioxidobenzo[d]thiazol-2-yl)sulfonyl)methyl)-5-chlorobenzo [4,5]isothiazolo[2,3-c][1,2,3]triazole 8,8-dioxide (4 e) and 3-(((5-bromo-1,1-dioxidobenzo[d]thiazol-2-yl)sulfonyl)methyl)-5-fluorobenzo [4,5] isothiazolo[2,3-c][1,2,3]triazole 8,8-dioxide (4 f) showed superior activity against A-549 and good activity against the MCF-7. Later, in vitro EGFR results revealed that compounds 4 e and 4 f indicated promising potency with IC50 values of 0.316 +/- 0.07 and 0.211 +/- 0.09 mu M respectively. In silico studies of five potent compounds were also carried out to identify interactions against EGFR receptors and found that the energy calculations were consistent with the IC50 values obtained. In silico pharmacokinetic profile was predicted for potent compounds 3 e, 3 f, 4 d, 4 e, and 4 f using SWISS/ADME and pkCSM, where, all the compounds followed the Lipinski rule without any deviation.

Automated summary

A one-step synthesis of fused Benzo[d]thiazolo-1,2,3-triazoles was developed using sulfonylazides and iodoalkyne. Several compounds showed superior activity against A-549 and good activity against MCF-7. In vitro and in silico studies demonstrated promising potency of the compounds against EGFR receptors.