新型邻苯二甲酰亚胺类似物的发现：合成、抗菌及抗结核筛选与分子对接研究

Discovery of novel phthalimide analogs: Synthesis, antimicrobial and antitubercular screening with molecular docking studies.

作者信息

Rateb Heba S, Ahmed Hany E A, Ahmed Sahar, Ihmaid Saleh, Afifi Tarek H

机构信息

Pharmacognosy and Pharmaceutical Chemistry Department, College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah 30001, Saudi Arabia; Department of Pharmaceutical and Medicinal Chemistry, Pharmacy College, Misr University for Science and Technology, Cairo, Egypt.

Pharmacognosy and Pharmaceutical Chemistry Department, College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah 30001, Saudi Arabia; Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt.

出版信息

EXCLI J. 2016 Dec 6;15:781-796. doi: 10.17179/excli2016-654. eCollection 2016.

In continuation of our endeavor towards the design and development of potent and effective antimicrobial agents, three series of phthalimide derivatives ( and ) were synthesized, fully characterized and evaluated for their potential antibacterial, antifungal and antimycobacterial activities. These efforts led to the discovery of nine compounds , and (MIC range from 0.49 to 31.5 μg/mL) with potent antibacterial, antifungal, and antimycobacterial activities. Ampicillin, ciprofloxacin, amphotericin B were used as references for antibacterial and antifungal screening respectively, while isoniazid was used as a reference for antimycobacterial testing. Furthermore, molecular modeling studies were done to explore the binding mode of the most active derivatives to M. tuberculosis enoyl reductase (InhA) and DNA gyrase B. Our study showed the importance of both hydrogen bonding and hydrophobic interactions as a key interaction with the target enzymes.

为持续致力于设计和开发强效且有效的抗菌剂，我们合成了三个系列的邻苯二甲酰亚胺衍生物（和），对其进行了全面表征，并评估了它们潜在的抗菌、抗真菌和抗分枝杆菌活性。这些研究工作发现了九种化合物（和，最低抑菌浓度范围为0.49至31.5μg/mL），它们具有强效的抗菌、抗真菌和抗分枝杆菌活性。氨苄西林、环丙沙星、两性霉素B分别用作抗菌和抗真菌筛选的对照，而异烟肼用作抗分枝杆菌测试的对照。此外，还进行了分子模拟研究，以探索活性最高的衍生物与结核分枝杆菌烯酰还原酶（InhA）和DNA促旋酶B的结合模式。我们的研究表明，氢键和疏水相互作用作为与靶酶的关键相互作用具有重要意义。