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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 μM 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.

A variety of novel tryptanthrin aminothiazole analogues 3a‐h and 5a‐h possessing a biologically active thiazole moiety were synthesized by the reaction of tryptanthrin thiosemicarbazones with different α‐bromo‐4‐substituted‐acetophenones compounds. The structures of all the synthesized compounds were characterized by mass, 1H NMR, 13C NMR, and elemental analysis. All the novel synthesized compounds were investigated for their in vitro anticancer activity against three human cancer cell lines (MCF‐7, A549, and HeLa) by taking cisplatin as a reference drug. The compounds 3b and 3c displayed excellent anticancer activities against the growth of three human cancer cell lines. EGFR targeting molecular docking investigation revealed that tryptanthrin aminothiazole analogues have better binding energies compared with EGFR inhibitors (Gefitinib, Erlotinib, and Lapatinib). The molecular docking findings back up the experimental anticancer activity results very well. The compounds were also tested for their antibacterial and antioxidant activities. In silico ADMT predictions have been performed that these tryptanthrin aminothiazole analogues have a good pharmacokinetic profile.

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