Department of Chemistry, Kurukshetra University, Kurukshetra, 136119, Haryana, India.
Council of Scientific and Industrial Research-National Institute of Science Communication and Policy Research, New Delhi, 110012, India.
ChemistryOpen. 2024 Nov;13(11):e202400142. doi: 10.1002/open.202400142. Epub 2024 Aug 8.
The present study describes an eco-friendly NBS-assisted regioselective synthesis of new 5-acylfunctionalized 5-acylfunctionalized 2-(1H-pyrazol-1-yl)thiazoles by condensation of 3,5-dimethyl-1H-pyrazole-1-carbothioamide with unsymmetrical 1,3-diketones under solvent-free conditions. The structural elucidation of the newly synthesized compounds was accomplished using various spectroscopic techniques viz. FTIR, NMR and mass spectrometry. All the newly synthesized compounds were examined for their in vitro antimicrobial potential against both pathogenic gram positive and gram negative bacterial and fungal species as well as anthelmintic activity against Pheretima posthuma earthworms. The results of antimicrobial activity revealed that all tested compounds 3 a-j showed excellent antimicrobial potential particularly against S. aureus. It was also observed that compounds 3 e and 3 i (MIC=62.5 μg/mL) showed greater potency against E. coli, whereas compounds 3 a and 3 h (MIC=50 μg/mL and 62.5 μg/mL) demonstrated better activity against P. aeruginosa and compound 3 i (MIC=62.5 μg/mL) exhibited superior activity against S. pyogenus when compared to standard drug Ampicillin (MIC=100μg/mL). Compound 3 e and 3 j revealed remarkable antifungal and anthelmintic activities. To find out binding interactions of target compounds with target proteins and pharmacokinetic parameters of the compounds, in silico investigations involving molecular docking studies and ADMET predictions were also performed.
本研究描述了一种环保的 NBS 辅助区域选择性合成新的 5-酰基功能化 5-酰基功能化 2-(1H-吡唑-1-基)噻唑的方法,方法是在无溶剂条件下,将 3,5-二甲基-1H-吡唑-1-碳硫酰胺与不对称 1,3-二酮缩合。新合成化合物的结构确证采用了各种光谱技术,如 FTIR、NMR 和质谱。所有新合成的化合物都进行了体外抗微生物活性测试,包括对革兰氏阳性和革兰氏阴性细菌和真菌以及对 Pheretima posthuma 蚯蚓的驱虫活性。抗菌活性结果表明,所有测试的化合物 3a-j 都表现出优异的抗菌潜力,特别是对金黄色葡萄球菌。还观察到化合物 3e 和 3i(MIC=62.5 μg/mL)对大肠杆菌的活性更强,而化合物 3a 和 3h(MIC=50 μg/mL 和 62.5 μg/mL)对铜绿假单胞菌的活性更好,化合物 3i(MIC=62.5 μg/mL)对化脓性链球菌的活性优于标准药物氨苄西林(MIC=100μg/mL)。化合物 3e 和 3j 表现出显著的抗真菌和驱虫活性。为了发现目标化合物与目标蛋白的结合相互作用和化合物的药代动力学参数,还进行了涉及分子对接研究和 ADMET 预测的计算机模拟研究。