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

Abstract

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.

Structural Insight into Groove Binding of Yohimbine with Calf Thymus DNA: A Spectroscopic, Calorimetric, and Computational Approach

“…Circular dichroism (CD) spectroscopy is an efficient method for examining the structural characteristics of DNA even during the interaction of small molecules with various kinds of DNA, such as A, B, Z, etc. , The point is that CD signals are a potent tool for determining the type of binding interactions and are highly sensitive. Indicated by a significant positive peak at 275 nm due to base stacking and a negative peak at 245 nm due to its helicity, canonical DNA conformation was observed in the CD spectrum of B-DNA (indicating the right-handed B-form of DNA) .…”

“…Information regarding the drug′s interaction with DNA upon binding is revealed through molecular modeling study . To understand the binding interactions, docking of the lowest-energy conformer of YH was performed with CT-DNA (PDB-ID: 1BNA) using the AutoDock 1.5.6 program. , …”

“…69 To understand the binding interactions, docking of the lowest-energy conformer of YH was performed with CT-DNA (PDB-ID: 1BNA) 88 using the AutoDock 1.5.6 program. 80,89 In each instance, docking was employed to highlight the YH binding interaction with the CT-DNA and to comprehend the underlying forces that are involved. YH compound was confirmed to exhibit a clear interaction with the naturally occurring polymeric CT-DNA, as shown in Figure 15.…”

Exploring the antioxidant, antimicrobial, cytotoxic and biothermodynamic properties of novel morpholine derivative bioactive Mn(ii), Co(ii) and Ni(ii) complexes – combined experimental and theoretical measurements towards DNA/BSA/SARS-CoV-2 3CLPro

“…Moreover, advanced DFT and molecular docking-based virtual screenings are quite helpful and will undoubtedly enhance our comprehension of the chemical and biological reactivity of medications. 19,20 Considering the above mentioned approach, the research scheme has been carried out using pharmacologically active morpholine-linked primary ligand and incorporated with 2,2' bipyridine for the synthesis of metal complexes (1)(2)(3) and extended the research to comprehend binding between the metal complexes (1-3) and DNA, BSA, and SARS-CoV-2 (3CL Pro ) protein via molecular docking approaches. They also might support the creation of new, powerful anticancer medications as well as the battle against current or prospective viral pandemics.…”

Electrochemical enaminone C–H thiolation/C–N amination cascade for thiazole synthesis and its diastereoselective dearomatization

“…9 As predetermined by the structure of thiocyanate salts, the diversity of the thiazole products associated with the thiocyanate substrate is restricted because no additional organic fragment can be brought to the product by the thiocyanate salt. In this context, several alternative sulfur-based building blocks such as xanthates, 10 dithioesters, 11 ureas, 12 thioamides, 13 and β-aminothiols 14 etc. have been used to construct the thiazole ring with suitable reaction partners.…”