Design, synthesis and characterization of tetra substituted 2,3-dihydrothiazole derivatives as DNA and BSA targeting agents: advantages of the visible-light-induced multicomponent approach

Abstract

This report describes the visible-light-induced one-pot multicomponent regioselective synthesis of a series of 5-aroyl-3-((arylidene)amino)-2-((arylidene)hydrazono)-4-methyl-2,3-dihydrothiazoles as DNA and BSA targeting agents. The multicomponent condensation of thiocarbohydrazide and aldehydes with α-bromo-1,3-diketones, generated in situ by the bromination of unsymmetrical 1,3-diketones with NBS using white LED light as an environmental friendly source in the presence of EtOAc solvent furnished the titled 2,3-dihydrothiazole derivatives in excellent yields. The exact regioisomeric structure was identified unambiguously by employing multinuclear 2D-NMR spectroscopy [¹H–¹³C] HMBC; [¹H–¹³C] HMQC and [¹H–¹⁵N] HMBC. Furthermore, the binding characteristics of the synthesized 2,3-dihydrothiazole derivatives were assessed with double-stranded calf-thymus DNA duplex (ct-DNA) and bovine serum albumin (BSA). Initial screening of all the synthesized 2,3-dihydrothiazole derivatives using various in silico techniques including molecular reactivity analysis, Lipinski rule and molecular docking, concluded 5-(4′-chlorobenzoyl)-3-((4′′-methoxybenzylidene)amino)-2-(4′′′-methoxybenzylidene)hydrazono)-4-methyl-2,3-dihydrothiazole derivative 6a as the most suitable compound for studying binding interaction with DNA and BSA. Additionally, to illustrate the ex vivo binding mode of 6a with DNA and BSA, several spectroscopic techniques viz. UV-visible, circular dichroism (CD), steady-state fluorescence and competitive displacement assays were carried out.