肼基连接的咪唑并[1,2 - ]嘧啶 - 噻唑杂化物：设计、合成及生物学评价研究 - Suppr

Hydrazineyl-linked imidazole[1,2-]pyrimidine-thiazole hybrids: design, synthesis, and biological evaluation studies.

作者信息

P Dinesha, Naik Shivakumar, D Udayakumar, B C Revanasiddappa, Ranjan Venkatesh, Veeranagaiah Naveena S

机构信息

Organic and Medicinal Chemistry Laboratory, Department of Chemistry, National Institute of Technology Karnataka Surathkal-575025 Mangalore Karnataka India

Department of Pharmaceutical Chemistry, NGSM Institute of Pharmaceutical Sciences Paneer, Deralakatte Mangalore-575018 Karnataka India.

出版信息

RSC Adv. 2025 Sep 8;15(39):32477-32496. doi: 10.1039/d5ra04692k. eCollection 2025 Sep 5.

This research work details the use of a molecular hybridization technique to create a library of four series of hydrazineyl-linked imidazo[1,2-]pyrimidine-thiazole derivatives. The structure of one of the final products, K2, was validated using single-crystal X-ray diffraction. Twenty-six novel hybrid molecules (K1-K26) were synthesized and tested for activity against the H37Rv strain. Three compounds (K1, K2, and K3) demonstrated significant inhibitory efficacy, with a MIC value of 1.6 μg mL. The target compounds also showed significant antibacterial activity against four bacterial strains, namely , , , and . In cytotoxicity studies using VERO cells, the potent -TB compounds (K1, K2, and K3) showed non-toxic profiles. Furthermore, ADME assessment results, molecular docking (against InhA and CYP121), and DFT studies revealed the active compounds' significant potential as scaffolds for novel antitubercular medicines.

本研究工作详细介绍了一种分子杂交技术的应用，以创建一个由四个系列的肼基连接的咪唑并[1,2 - ]嘧啶 - 噻唑衍生物组成的文库。使用单晶X射线衍射对最终产物之一K2的结构进行了验证。合成了26种新型杂化分子（K1 - K26），并测试了它们对H37Rv菌株的活性。三种化合物（K1、K2和K3）表现出显著的抑制效果，最低抑菌浓度（MIC）值为1.6 μg/mL。目标化合物对四种细菌菌株，即、、和也表现出显著的抗菌活性。在使用VERO细胞进行的细胞毒性研究中，强效抗结核化合物（K1、K2和K3）显示出无毒特征。此外，药物代谢动力学（ADME）评估结果、分子对接（针对InhA和CYP121）以及密度泛函理论（DFT）研究表明，这些活性化合物作为新型抗结核药物的支架具有巨大潜力。