Current Issue : April-June Volume : 2026 Issue Number : 2 Articles : 5 Articles
Imidazothiazoles are important and attractive scaffolds for the design of potential biologically active small molecules. Dialkylenamines are convenient building blocks and are often used as intermediate reagents for the synthesis of various heterocyclic systems such as pyrimidine, pyridine, pyrazole, etc. In the present paper, the simple and effective synthesis of (Z)-6-((dimethylamino)methylene)-2-methyl-2,3-dihydroimidazo[2,1-b]thiazol- 5(6H)-one (2) is reported. The proposed method, based on the reflux of 2-methyl-2,3- dihydroimidazo[2,1-b]thiazol-5(6H)-one with N,N-dimethylformamide dimethyl acetal, leads to an 80% yield of title compound 2. The structure of the synthesized compound 2 was confirmed using 1H, 13C NMR, and LC-MS spectra. The applied protocol demonstrates practical advantages such as the absence of a solvent, a simple work-up, and the possibility of scale-up....
Using virtual FragLites screening and a fragment-based drug discovery (FBDD) strategy, we designed and synthesized a series of 6-substituted-1-(3,4,5-trimethoxyphe-nyl)-1H-indole derivatives as potential tubulin polymerization inhibitors. Among them, compound 3g exhibited the best antiproliferative activity within this series and affected microtubule dynamics in a concentration-dependent manner. Further studies indicated that 3g induced G2/M cell-cycle arrest and triggered apoptosis in MCF-7 cells. In vivo, 3g achieved tumor growth inhibition rates of 23.3% and 44.2% at 20 mg/kg and 50 mg/kg, respectively, without evident systemic toxicity. These results suggest that 3g shows preliminary antitumor efficacy and may serve as a starting point for further mechanistic and structural studies. Further optimization and detailed pharmacokinetic and toxicity studies are merited to advance these inhibitors in preclinical development....
Inhibition of glycogen phosphorylases (GP) has been regarded as a therapeutic strategy for blood glucose control in diabetes. In this study, a series of novel dibenzoxazepinone derivatives was synthesized. The in vitro activity screening results indicated that compound Id most signicantly inhibited glycogen phosphorylase (GP) activity, with an IC50 of 266 ± 1 nM, which was superior to the positive control drug PSN-357, a Phase II clinical GP inhibitor from Japan’s OSI Corporation. In vivo experiments showed that Id could significantly reduce blood glucose levels in adrenaline-induced acute hyperglycemic mice and high-fat-diet-induced obese and diabetic (DIO) mice....
Hybrid molecules, integrating multiple pharmacophores within a single scaffold, represent a modern strategy in drug discovery, offering improved selectivity and safety. Anthranilic acid is a versatile building block with diverse biological activities. In this work, we designed and synthesized novel anthranilic acid-based hybrids with enhanced pharmacokinetic potential. The methods used include cheminformatics- guided library design, followed by amide bond formation between anthranilic acid derivatives and substituted 2-phenylethylamines. Purification and structural characterization were achieved via NMR, IR, and HRMS. The compounds exhibited favorable, predicted ADME/Tox profiles and synthetic accessibility. These results provide a foundation for further biological evaluation toward therapies for smooth muscle dysfunction and inflammation....
Breast cancer remains the most frequently diagnosed malignant tumor among women worldwide, and the limited selectivity as well as the emerging resistance to currently used therapies highlight the need to search for new therapeutic compounds. Aromatase, a key enzyme in the estrogen biosynthesis pathway, represents a recognized molecular target in the treatment of hormone-dependent cancers. In this study, six new 1,3,4-thiadiazole derivatives containing two halogen-substituted aromatic rings were designed and synthesized as potential nonsteroidal aromatase inhibitors. The cytotoxic activity of the obtained compounds was evaluated against two breast cancer cell lines: MCF-7 (estrogen-dependent) and MDA-MB-231 (estrogen-independent). All tested compounds exhibited concentrationdependent cytotoxic activity against MCF-7 cells, with the strongest effects observed for compounds A2, A3, B1, and B3 (IC50 ≈ 52–55 μM). In contrast, none of the tested compounds showed significant activity against MDA-MB-231 cells (IC50 > 100 μM), suggesting their selectivity toward estrogen-dependent cancer cells. Compound B3, identified as the most promising, was further subjected to in silico analyses. Molecular docking and molecular dynamics simulations revealed that B3 occupies a binding site similar to that of the co-crystallized native inhibitor and forms interactions characteristic of strong aromatase inhibitors. The obtained results confirm a mechanism of action related to aromatase inhibition and indicate that fluorophenyl-substituted 1,3,4-thiadiazole derivatives represent a promising scaffold for the design of new, selective, and less toxic aromatase inhibitors....
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