在目前的工作中,从4-乙酰基-1,3-二苯基-1H-吡唑-5(4H)-ole1合成了两个杂化系列的吡唑簇状嘧啶和吡唑簇状噻唑化合物3-21作为新型抗菌剂。它们的化学结构在光谱分析方面得到了彻底的阐明,如IR,1HNMR,13CNMR和质谱。在体外评估化合物对各种标准病原体菌株的抗微生物效率。革兰氏细菌(铜绿假单胞菌,肺炎克雷伯菌),革兰氏+ive细菌(MRSA,枯草芽孢杆菌),和单细胞真菌(白色念珠菌)微生物。ZOI结果显示大多数测试的分子表现出从中等到高的抑制效力。其中与标准药物相比,化合物7、8、12、13和19表现出对大多数测试的病原微生物的最高抑制效力。此外,MIC结果表明,最有效的分子7、8、12、13和19在低浓度时对大多数测试微生物显示出抑制作用。此外,进行了新合成的化合物对DNA促旋酶的对接方法,以更深入地研究其抗菌功效的分子机制。Further,进行计算研究以计算化合物的药代动力学参数。其中7、8、12、13和19是最有效的化合物,与标准药物相比,对大多数测试的病原微生物显示出最高的抑制效力。
In the present work, two hybrid series of
pyrazole-clubbed pyrimidine and
pyrazole-clubbed thiazole compounds 3-21 from 4-acetyl-1,3-diphenyl-1H-
pyrazole-5(4H)-ole 1 were synthesized as novel antimicrobial agents. Their chemical structures were thoroughly elucidated in terms of spectral analyses such as IR, 1H NMR, 13C NMR and mass spectra. The compounds were in vitro evaluated for their antimicrobial efficiency against various standard pathogen strains, gram -ive bacteria (Pseudomonas aeruginosa, Klebsiella pneumonia), gram + ive bacteria (MRSA, Bacillus subtilis), and Unicellular fungi (Candida albicans) microorganisms. The ZOI results exhibited that most of the tested molecules exhibited inhibition potency from moderate to high. Where compounds 7, 8, 12, 13 and 19 represented the highest inhibition potency against most of the tested pathogenic microbes comparing with the standard drugs. In addition, the MIC results showed that the most potent molecules 7, 8, 12, 13 and 19 showed inhibition effect against most of the tested microbes at low concentration. Moreover, the docking approach of the newly synthesized compounds against DNA gyrase enzyme was performed to go deeper into their molecular mechanism of antimicrobial efficacy. Further, computational investigations to calculate the pharmacokinetics parameters of the compounds were performed. Among them 7, 8, 12, 13 and 19 are the most potent compounds revealed the highest inhibition efficacy against most of the tested pathogenic microbes comparing with the standard drugs.