Tiwari Deeksha, Narang Rakesh, Sudhakar Kalvatala, Singh Vikramjeet, Lal Sukhbir, Devgun Manish
Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, India.
School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, India.
Chem Biol Drug Des. 2022 Dec;100(6):1086-1121. doi: 10.1111/cbdd.14100. Epub 2022 Jun 27.
Due to the emergence of drug-resistant microbial strains, different research groups are continuously developing novel drug molecules against already exploited and unexploited targets. 1,3,4-Oxadiazole derivatives exhibited noteworthy antimicrobial activities. The presence of 1,3,4-oxadiazole moiety in antimicrobial agents can modify their polarity and flexibility, which significantly improves biological activities due to various bonded and non-bonded interactions viz. hydrogen bond, steric, electrostatic, and hydrophobic with target sites. The present review elaborates the therapeutic targets and mode of interaction of 1,3,4-oxadiazoles as antimicrobial agents. 1,3,4-oxadiazole derivatives target enoyl reductase (InhA), 14α-demethylase in the mycobacterial cell; GlcN-6-P synthase, thymidylate synthase, peptide deformylase, RNA polymerase, dehydrosqualene synthase in bacterial strains; ergosterol biosynthesis pathway, P450-14α demethylase, protein-N-myristoyltransferase in fungal strains; FtsZ protein, interfere with purine and functional protein synthesis in plant bacteria. The present review also summarizes the effect of different moieties and functional groups on the antimicrobial activity of 1,3,4-oxadiazole derivatives.
由于耐药微生物菌株的出现,不同的研究小组正在不断开发针对已被利用和未被利用靶点的新型药物分子。1,3,4-恶二唑衍生物表现出显著的抗菌活性。抗菌剂中1,3,4-恶二唑部分的存在可以改变其极性和柔韧性,由于与靶点部位的各种键合和非键合相互作用,即氢键、空间、静电和疏水作用,从而显著提高生物活性。本综述阐述了1,3,4-恶二唑作为抗菌剂的治疗靶点和相互作用模式。1,3,4-恶二唑衍生物靶向分枝杆菌细胞中的烯酰还原酶(InhA)、14α-脱甲基酶;细菌菌株中的葡糖胺-6-磷酸合酶、胸苷酸合酶、肽脱甲酰基酶、RNA聚合酶、脱水鲨烯合酶;真菌菌株中的麦角固醇生物合成途径、P450-14α脱甲基酶、蛋白质N-肉豆蔻酰转移酶;FtsZ蛋白,干扰植物细菌中的嘌呤和功能蛋白合成。本综述还总结了不同基团和官能团对1,3,4-恶二唑衍生物抗菌活性的影响。