El-Sayed Selwan M, Ahmed Samar A, Gulia Kanika, Lenhard Justin R, Hassan Ahmed H E, Farahat Abdelbasset A
Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 35712, Egypt.
Pharmaceuticals (Basel). 2023 Jul 22;16(7):1040. doi: 10.3390/ph16071040.
The continuing need for the discovery of potent antibacterial agents against antibiotic-resistant pathogens is the driving force for many researchers to design and develop such agents. Herein, we report the design, synthesis, and biological evaluation of amidine derivatives as new antibacterial agents. Compound was the most active in this study against a wide range of antibiotic-resistant, and susceptible, Gram-positive, and Gram-negative bacterial strains. Time-kill assay experiments indicated that compound was an effective bactericidal compound against the tested organisms at the log-phase of bacterial growth. Docking simulations were performed to assess its mode of action regarding UPPS, KARI, and DNA as potential bacterial targets. Results unveiled the importance of structural features of compound in its biological activity including central thiophene ring equipped with left and right pyrrolo[2,3-]pyridine and phenyl moieties and two terminal amidines cyclized into 4,5-dihydro-1-imidazol-2-yl functionalities. Collectively, compound represents a possible hit for future development of potent antibacterial agents.
持续需要发现针对抗生素耐药病原体的强效抗菌剂，这是许多研究人员设计和开发此类药剂的驱动力。在此，我们报告脒衍生物作为新型抗菌剂的设计、合成及生物学评价。化合物 在本研究中对多种抗生素耐药及敏感的革兰氏阳性和革兰氏阴性菌株表现出最强活性。时间杀菌试验实验表明，化合物 在细菌生长对数期对受试生物体是一种有效的杀菌化合物。进行对接模拟以评估其针对UPPS、KARI和DNA作为潜在细菌靶点的作用模式。结果揭示了化合物 的结构特征在其生物活性中的重要性，包括配备左右吡咯并[2,3 - ]吡啶和苯基部分的中心噻吩环以及环化为4,5 - 二氢 - 1 - 咪唑 - 2 - 基官能团的两个末端脒。总体而言，化合物 代表了未来开发强效抗菌剂的一个可能的切入点。
