Soliman Dalia Hussein, Eldehna Wagdy Mohamed, Ghabbour Hazem Ahmed, Kabil Maha Mamdouh, Abdel-Aziz Marwa Mostafa, Abdel-Aziz Hatem Abdel-Kader
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University.
Pharmaceutical Chemistry Department, Faculty of Pharmacy (Girls), Al-Azhar University.
Biol Pharm Bull. 2017;40(11):1883-1893. doi: 10.1248/bpb.b17-00361.
In our ongoing efforts to develop potent antitubercular agents based on the 6-phenylnicotinohydrazide, herein we report the design, synthesis and biological evaluation of three sets of 6-phenylnicotinohydrazide derivatives 8a-g, 12 and 16a, b. The designed compounds were synthesized and in vitro evaluated for their antitubercular activity. In addition, their antifungal and antibacterial activities were evaluated as well. The nicotinohydrazide class displayed different levels of antimicrobial activity and possessed a distinctive pattern of selectivity against the tested microorganisms. However, the 2,6-dichlorobenzylidene counterpart 8b emerged as the most active one in this study, with superior antimycobacterial activity (minimum inhibitory concentration (MIC)=3.90 µg/mL) and potent broad-spectrum antimicrobial activities with MIC range of 0.24-1.95 µg/mL. The structure-activity relationship for such nicotinohydrazides has been established. Further, the cytotoxicity of the most active antitubercular compounds 8b, d and g were tested against the normal breast cells WI-38; none of them displayed significant cytotoxic effect, thereby providing a good therapeutic index.
在我们持续致力于开发基于6-苯基烟酰肼的强效抗结核药物的过程中，在此我们报告了三组6-苯基烟酰肼衍生物8a - g、12和16a、b的设计、合成及生物学评价。所设计的化合物被合成出来并对其抗结核活性进行了体外评估。此外，还评估了它们的抗真菌和抗菌活性。烟酰肼类显示出不同水平的抗菌活性，并且对受试微生物具有独特的选择性模式。然而，2,6 - 二氯亚苄基类似物8b在本研究中成为活性最高的化合物，具有卓越的抗分枝杆菌活性（最低抑菌浓度（MIC）=3.90 µg/mL）以及MIC范围为0.24 - 1.95 µg/mL的强效广谱抗菌活性。已建立了此类烟酰肼的构效关系。此外，对活性最高的抗结核化合物8b、d和g针对正常乳腺细胞WI - 38进行了细胞毒性测试；它们均未显示出显著的细胞毒性作用，从而提供了良好的治疗指数。
