Abstract

Reaction of isoquinoline 1 with hydrazonoyl chlorides 2A–E gave the corresponding triazoloisoquinolines 4A–E. The latter products 4A–E were reacted with 4-(piperidin-1-yl)benzaldehyde 5a and 4-morpholinobenzaldehyde 5b to afford the corresponding chalcones 6a,b. Some of chalcones 6 were reacted with hydrazine hydrate in refluxing ethanol to give the corresponding 8,9-dimethoxy-1-aryl-4,5-dihydro-1H-pyrazol-3-yl-1,5,6,10b-tetrahydro-[1,2,4]triazolo[3,4-a]isoquinoline derivatives 7A–C. Antimicrobial studies were performed using gram-negative bacteria (Escherichia coli) and (Klebsiella pneumonia), a gram-positive bacteria (Streptococcus mutans) and (Staphylococcus aureus), filamentous fungus (Asperagillus Nigar) and yeast (Candida albicans). Data revealed that chalcone 6Aa achieved the lowest MIC values (high efficient derivative) against the sensitive bacterial strain E. coli with MIC value 130 µg/ml. The most effective compound 6Aa, which demonstrated the highest binding affinity toward tested protein [thymidine phosphorylase enzyme, (PDB ID:4EAD)], was docked using MOE 2014.09 software.

摘要

异喹啉1与肼酰氯2A-E反应生成相应的三唑并异喹啉4A-E。后一种产物4A-E与 4-(哌啶-1-基)苯甲醛5a和 4-吗啉代苯甲醛5b反应得到相应的查耳酮6a,b。一些查尔酮6在回流乙醇中与水合肼反应，得到相应的 8,9-dimethoxy-1-aryl-4,5-dihydro-1 H -pyrazol-3-yl-1,5,6,10 b -四氢-[1,2,4]三唑并[3,4- a ]异喹啉衍生物7A–C. 使用革兰氏阴性菌（大肠杆菌）和（肺炎克雷伯菌）、革兰氏阳性菌（变形链球菌）和（金黄色葡萄球菌）、丝状真菌（黑曲霉）和酵母（白色念珠菌）进行抗菌研究。数据显示，查尔酮6Aa对敏感菌株大肠杆菌的MIC值最低（高效衍生物），MIC值为130 µg/ml。最有效的化合物6Aa使用 MOE 2014.09 软件对接显示对测试蛋白质 [胸苷磷酸化酶，(PDB ID:4EAD)] 的最高结合亲和力。