Green Synthesis, Experimental and Theoretical Studies to Discover Novel Binders of Exosomal Tetraspanin CD81 Protein

[Image: see text] A new class of benzothiazole-appended quinoline derivatives (6–8) was synthesized via one-pot TPGS micellar-mediated acid-catalyzed nucleophilic addition, followed by aerobic oxidative cyclization of 3-formylquinoline-2-one (2), 3-formylquinoline-2-thione (3), and 2-azidoquinoline-3-carbaldehyde (4) individually with 2-amino thiophenol (5). The structures of the prepared compounds were confirmed using suitable spectroscopic methods complemented with single-crystal X-ray diffraction analysis. Time-dependent density functional theory-based optimization of molecular structures, bond lengths, bond angles, HOMO–LUMO energy gaps, and molecular electrostatic potential maps was theoretically computed at the B3LYP/6-311++g(d) level. The molecular docking studies recommended that 6–8 bound to the active site cavity of CD81 effectively with the binding energies of −6.9, −6.3, and −6.5 kcal mol(–1), respectively. Further, MD simulation studies of compound 6 suggested that the binding resulted in the stabilization of the CD81 molecule. Thus, all theoretical predictions associated with the experimental verifications motivated to discover novel approaches for cancer therapy.