Visible Light-Prompted Regioselective Synthesis of Novel 5-Aroyl/hetaroyl-2',4-dimethyl-2,4'-bithiazoles as DNA- and BSA-Targeting Agents

Abstract

Organic transformations mediated by visible light have gained popularity in recent years as they are green, renewable, inexpensive, and clean and yield excellent products. The present study describes cyclo-condensation of 2-methylthiazole-4-carbothioamide with differently substituted α-bromo-1,3-diketones achieved by utilizing a white light-emitting diode (LED) (9W) to accomplish the regioselective synthesis of novel 5-aroyl/hetaroyl-2',4-dimethyl-2,4'-bithiazole derivatives as DNA/bovine serum albumin (BSA)-targeting agents. The structure characterization of the exact regioisomer was achieved unequivocally by heteronuclear two-dimensional nuclear magnetic resonance (2D-NMR) spectroscopy [¹H-¹³C] HMBC; [¹H-¹³C] HMQC; and [¹H-¹⁵N] HMBC. In silico toxicity studies indicated that the synthesized compounds exhibit low toxicity risks and adhere to the rules of oral bioavailability without any exception. Computational molecular modeling of the bithiazole derivatives with the dodecamer sequence of the DNA duplex and BSA identified 5-(4-chlorobenzoyl)-2',4-dimethyl-2,4'-bithiazole 7g as the most suitable derivative that can interact effectively with these biomolecules. Furthermore, theoretical results concurred with the ex vivo binding mode of the 7g with calf thymus DNA (ct-DNA) and BSA through a variety of spectroscopic techniques, viz., ultraviolet-visible (UV-visible), circular dichroism (CD), steady-state fluorescence, and competitive displacement assay, along with viscosity measurements.