Visible-Light-Prompted Synthesis and Binding Studies of 5,6-Dihydroimidazo[2,1‑b]thiazoles with BSA and DNA Using Biophysical and Computational Methods

• Published in: Journal of organic chemistry 2022-03, Vol.87 (6), p.3952-3966
• Main Authors: Aggarwal, Ranjana, Hooda, Mona, Kumar, Prince, Jain, Naman, Dubey, Gyan Prakash, Chugh, Heerak, Chandra, Ramesh
• Format: Article
• Language: English
• Subjects: Binding Sites; Circular Dichroism; DNA; Molecular Docking Simulation; Protein Binding; Serum Albumin, Bovine - chemistry; Spectrometry, Fluorescence; Thermodynamics; Thiazoles
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.1c02471

Fused heterocyclic systems containing a bridgehead nitrogen atom have emerged as imperative pharmacophores in the design and development of new drugs. Among these heterocyclic moieties, the imidazothiazole scaffold has long been used in medicinal chemistry for the treatment of various diseases. In this study, we have established a simplistic and environmentally safe regioselective protocol for the synthesis of 5,6-dihydroimidazo­[2,1-b]­thiazole derivatives from easily available reactants. The reaction proceeds through in situ formation of the α-bromodiketones ensuing trap with imidazolidine-2-thione to provide these versatile bicyclic heterocycles in excellent yields. The synthesized compounds were screened through the molecular docking approach for the most stable complex formation with bovine serum albumin (BSA) and calf thymus deoxyribonucleic acid (ctDNA). The selected compound was further studied using ex vivo binding studies, which revealed moderate interactions with BSA and ctDNA. The binding studies were performed using biophysical approaches including UV–visible spectroscopy, steady-state fluorescence, circular dichroism (CD), and viscosity parameters.