In recent times, fused azaheterocycles emerged as impressive therapeutic agents. Binding studies of such azaheterocycles with biomolecules is an important subject for pharmaceutical and biochemical studies aiming at the design and development of new drugs. Fused heterocyclic scaffolds, such as thiazolopyrmidines have long been used in the pharmaceutical industry for the treatment of various diseases. In this study, we have accomplished a regioselective synthesis of 2-aroyl-3-methyl-6,7-dihydro-5H-thiazolo[3,2-a]pyrimidines by the reaction of tetrahydropyrimidine-2(H)-thione with α-bromo-1,3-diketones, generated in situ from 1,3-diketones and NBS, using visible light as an inexpensive, green and renewable energy source under mild reaction conditions with wide-ranging substrate scope. The regioisomer was characterized unambiguously by 2D-NMR [1H-13C] HMBC and [1H-13C] HMQC spectroscopy. In silico toxicity data analysis showed the low toxicity risks of the synthesized compounds. Computational molecular docking studies were carried out to examine the interaction of thiazolo[3,2-a]pyrimidines with calf-thymus DNA (ct-DNA) and Bovine Serum Albumin (BSA). Moreover, different spectroscopic approaches viz. steady-state fluorescence, competitive displacement assay, UV–visible and circular dichroism (CD) along with viscosity measurements were employed to investigate the binding mechanisms of thiazolo[3,2-a]pyrimidines with DNA and BSA. The results thus obtained revealed that thiazolo[3,2-a]pyrimidines offer groove bindings with DNA and showed moderate bindings with BSA.

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.

From a green chemistry perspective, sustainable irradiations as the power source and water as solvent have certainly grabbed the attention of chemists in recent times as these efforts reduce hazardous...

The present review article strives to compile the latest synthetic approaches for the synthesis of triazolothiadiazine and its derivatives, along with their diverse pharmacological activities, viz. anticancer, antimicrobial, analgesic and anti-inflammatory, antioxidant, antiviral, enzyme inhibitors (carbonic anhydrase inhibitors, cholinesterase inhibitors, alkaline phosphatase inhibitors, anti-lipase activity, and aromatase inhibitors) and antitubercular agents. The review focuses particularly on the structure–activity relationship of biologically important 1,2,4-triazolo[3,4- b ][1,3,4]thiadiazines, which have profound importance in drug design, discovery and development. In silico pharmacokinetic and molecular modeling studies have also been summarized. It is hoped that this review article will be of help to researchers engaged in the development of new biologically active entities for the rational design and development of new target-oriented 1,2,4-triazolo[3,4- b ][1,3,4]thiadiazine-based drugs for the treatment of multifunctional diseases. Graphical Abstract

To meet the growing need for stable and clinically effective chemotherapeutic agents, herein, we have synthesized a series of acyl‐functionalized thiazolo[3,2‐b]‐[1,2,4]triazole derivatives in highly efficient and regioselective manner. The structure of newly synthesized regioisomeric products was unambiguously characterized by multinuclear 2D‐NMR [(1H−13C) HMBC, (1H−13C) HMQC] spectroscopic data. To assess the anticancer and pharmacokinetic profile of the synthesized compounds, we performed in silico, and ex vivo binding studies of compounds with calf‐thymus deoxyribonucleic acid (ct‐DNA) and bovine serum albumin (BSA), respectively, and also tested their efficacy against five human cancer cell lines. viz., MCF‐7 (breast cancer), BT‐474 (breast cancer), A549 (lung cancer), MOLT4 (acute lymphoblastic leukemia), and BxPC3 (pancreatic cancer). Compounds (2‐(4‐chlorophenyl)‐6‐methylthiazolo[3,2‐b][1,2,4]triazol‐5‐yl)(4‐fluorophenyl)methanone 6 l, (4‐chlorophenyl)(2‐(4‐chlorophenyl)‐6‐methylthiazolo[3,2‐b][1,2,4]triazol‐5‐yl)methanone 6 m and (2‐(4‐chlorophenyl)‐6‐methylthiazolo[3,2‐b][1,2,4]triazol‐5‐yl)(4‐methoxyphenyl) methanone 6 q exhibited excellent anticancer potential among the screened derivatives. Furthermore, ex‐vivo mechanistic investigations showed the static mode of quenching and moderate bindings between the ligand and biomolecules; DNA (Kq=2.01‐2.24*1012 M−1 s−1) and BSA (Kq=2.25‐.2.72*1012 M−1 s−1). Moreover, fluorescence displacement assay demonstrated a groove binding mode of interaction with ct‐DNA, which was supported by UV‐Visible absorption spectrum, circular dichroism, and viscosity analysis.