Novel tryptanthrin hybrids bearing aminothiazoles as potential EGFR inhibitors: Design, synthesis, biological screening, molecular docking studies, and ADME/T predictions

Abstract

AbstractA 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.