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首页> 外文期刊>Medicinal chemistry >Novel phthalazinyl derivatives: synthesis, antimycobacterial activities, and inhibition of Mycobacterium tuberculosis isocitrate lyase enzyme.
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Novel phthalazinyl derivatives: synthesis, antimycobacterial activities, and inhibition of Mycobacterium tuberculosis isocitrate lyase enzyme.

机译：新型酞嗪衍生物：合成，抗分枝杆菌活性和对结核分枝杆菌异柠檬酸裂合酶的抑制作用。

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摘要

Novel 2-[3-(4-bromo-2-fluorobenzyl)-4-oxo-3,4-dihydro-1-phthalazinyl]acetic acid hydrazones were synthesized from phthalic anhydride by a six step synthesis and evaluated for in vitro, in vivo activities against eight mycobacterial species and Mycobacterium tuberculosis (MTB) isocitrate lyase (ICL) enzyme inhibition studies. Among twenty six compounds N'1-[(4-nitrophenyl)methylene]-2-[3-(4-bromo-2-fluorobenzyl)-4-oxo-1,2,3,4-tetrah ydro-1-phthalazinyl]ethanohydrazide (7j) was found to be the most active compound in-vitro with MIC's of 0.18 and <0.09 microM against log-phase cultures of MTB and multi-drug resistant MTB respectively. Compound 7j inhibited all the eight mycobacterial species with MIC ranging from <0.09-12.25 microM and was not toxic to Vero cell lines till 122.5 microM. Seven compounds were tested against starved culture of MTB and they inhibited with MIC's ranging from 2.88-8.91 microM. Some compounds showed 45-61% inhibition against MTB ICL enzyme at 10 microM. In the in vivo animal model 7j decreased the bacterial load in lung and spleen tissues with 1.87 and 3.03-log10 protections respectively at 25 mg/kg body weight dose.
机译：新型的2- [3-（4-溴-2-氟苄基）-4-氧代-3,4-二氢-1-酞嗪基]乙酸盐是由邻苯二甲酸酐通过六步合成法合成的，并在体外进行了评价。体内针对八种分枝杆菌物种和结核分枝杆菌（MTB）异柠檬酸裂合酶（ICL）酶抑制活性的研究。在二十六个化合物中，N'1-[（4-硝基苯基）亚甲基] -2- [3-（4-溴-2-氟苄基）-4-氧-1,2,3,4-四氢-1-酞嗪基发现乙酰肼（7j）是体外活性最高的化合物，其对MTB和耐多药MTB的对数期培养的MIC分别为0.18和<0.09 microM。化合物7j抑制所有8种分枝杆菌，MIC的范围为<0.09-12.25 microM，对Vero细胞系无毒，直至122.5 microM。测试了七种化合物对MTB饥饿培养的抑制作用，它们的MIC抑制范围为2.88-8.91 microM。一些化合物在10 microM时对MTB ICL酶显示45-61％的抑制作用。在体内动物模型7j中，在剂量为25 mg / kg体重时，分别以1.87和3.03-log10的保护作用降低了肺和脾脏组织中的细菌载量。

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