Al-Wahaibi Lamya H, Rabea Safwat M, Mahmoud Mohamed A, Youssif Bahaa G M, Bräse Stefan, Abdel-Aziz Salah A
Department of Chemistry, College of Sciences, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia.
Medicinal Chemistry Department, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
ACS Omega. 2024 Nov 11;9(47):47261-47273. doi: 10.1021/acsomega.4c08365. eCollection 2024 Nov 26.
A series of 1,2,4-triazolo[1,5-]pyrimidine-based derivatives were developed and prepared by reacting chalcones - with 3-phenyl-1,2,4-triazole-5-amine (). The novel compounds were analyzed using several spectroscopic techniques, and their antimicrobial efficacies against six pathogens (Gram-negative, Gram-positive, and fungi) were tested. Most of the tested compounds exhibited significant antimicrobial activity compared to ciprofloxacin and fluconazole. Four compounds (, , , and ) showed promising results. Their minimal inhibitory concentration (MIC) values were between 16 and 102 μM, similar to ciprofloxacin's 10-90 μM values. MIC values against the tested fungal species were between 15.50 and 26.30 μM, higher than fluconazole's 11.50-17.50 μM values. Compounds and , in particular, showed excellent bactericidal activity. Compounds and , the most effective antibacterial agents, were further evaluated for their inhibitory effects on bacterial DNA gyrase and DHFR enzymes as possible molecular targets. The results indicated that and demonstrated a similar level of activity against DNA gyrase and DHFR when compared to the reference drugs ciprofloxacin and trimethoprim. We conducted molecular docking to investigate the binding mechanism and evaluate the reactivity of the intriguing compounds. Compounds and demonstrated favorable binding interactions with the essential amino acids necessary for the inhibition of DNA gyrase and DHFR enzymes.
通过查尔酮与3-苯基-1,2,4-三唑-5-胺反应，开发并制备了一系列基于1,2,4-三唑并[1,5 -]嘧啶的衍生物。使用多种光谱技术对这些新型化合物进行了分析，并测试了它们对六种病原体（革兰氏阴性菌、革兰氏阳性菌和真菌）的抗菌效果。与环丙沙星和氟康唑相比，大多数测试化合物表现出显著的抗菌活性。四种化合物（、、和）显示出有前景的结果。它们的最低抑菌浓度（MIC）值在16至102μM之间，与环丙沙星的10 - 90μM值相似。对测试真菌物种的MIC值在15.50至26.30μM之间，高于氟康唑的11.50 - 17.50μM值。特别是化合物和表现出优异的杀菌活性。化合物和这两种最有效的抗菌剂，作为可能的分子靶点，进一步评估了它们对细菌DNA促旋酶和二氢叶酸还原酶（DHFR）的抑制作用。结果表明，与参考药物环丙沙星和甲氧苄啶相比，和对DNA促旋酶和DHFR表现出相似水平的活性。我们进行了分子对接，以研究结合机制并评估这些有趣化合物的反应性。化合物和与抑制DNA促旋酶和DHFR酶所需的必需氨基酸表现出良好的结合相互作用。
