Sharma Vishal, Das Rina, Mehta Dinesh Kumar, Sharma Diksha
Department of Pharmaceutical Chemistry, MM College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, 133207, India.
Swami Devidyal College of Pharmacy, Barwala, 134118, India.
Mol Divers. 2025 Jun;29(3):1911-1928. doi: 10.1007/s11030-024-10949-y. Epub 2024 Aug 3.
A novel series of quinolone-substituted 1,3,4-oxadiazole derivatives 4(a-l) have been designed and synthesized. The target compounds were investigated for their antibacterial activity against gram positive (Staphylococcus aureus, ATCC 25923, Enterococcus faecalis, ATCC 29212) and gram negative bacterium (Escherichia coli, ATCC 25922, Pseudomonas aeruginosa, ATCC 27853) for antifungal activity using (Candida albicans, ATCC 10231) and anti-inflammatory activity as COX-II inhibitors, respectively. The 1,3,4-oxadiazole functionality was introduced at C-6 position of pipemidic acid derivatives. IR, H NMR and Mass spectrometry techniques confirmed the structure of synthesized derivatives. The quinolone (pipemidic acid)-oxadiazole hybrid derivatives were effective against bacterial strains. When compared to ciprofloxacin (MIC 16 µg/mL), the compounds under consideration (4f, 4h, and 4k) showed significant antibacterial activity against all bacterial strains except Enterococcus faecalis, with MICs of 8 µg/mL. On the other hand, synthesized target compounds 4(a-l) did not respond well against Candida albicans fungal strain. The compound (4k) represents high % inhibition against COX-II. The compounds (4f, 4h and 4k) exhibited highest hydrogen bonding interaction with ARG57, ARG72, ARG78, LEU54 and MET16 target residues with a binding energy of - 8.4, - 8.6 and - 8.5 kcal/mol into the active pocket of DNA gyrase enzyme respectively even better in comparison to reference ligands. Based on the docking study, quinolone (pipemidic acid) oxadiazole hybrid structural ligands exhibited strong interaction at binding pockets of DNA gyrase enzyme.
设计并合成了一系列新型喹诺酮取代的1,3,4-恶二唑衍生物4(a-l)。分别研究了目标化合物对革兰氏阳性菌（金黄色葡萄球菌、ATCC 25923、粪肠球菌、ATCC 29212）和革兰氏阴性菌（大肠杆菌、ATCC 25922、铜绿假单胞菌、ATCC 27853）的抗菌活性，对白色念珠菌（ATCC 10231）的抗真菌活性以及作为COX-II抑制剂的抗炎活性。在吡哌酸衍生物的C-6位引入了1,3,4-恶二唑官能团。红外光谱、核磁共振氢谱和质谱技术证实了合成衍生物的结构。喹诺酮（吡哌酸）-恶二唑杂化衍生物对细菌菌株有效。与环丙沙星（MIC为16 μg/mL）相比，所研究的化合物（4f、4h和4k）对除粪肠球菌外的所有细菌菌株均表现出显著的抗菌活性，MIC为8 μg/mL。另一方面，合成的目标化合物4(a-l)对白色念珠菌真菌菌株反应不佳。化合物（4k）对COX-II表现出较高的抑制率。化合物（4f、4h和4k）与ARG57、ARG72、ARG78、LEU54和MET16目标残基表现出最强的氢键相互作用，结合能分别为-8.4、-8.6和-8.5 kcal/mol，进入DNA促旋酶的活性口袋，与参考配体相比甚至更好。基于对接研究，喹诺酮（吡哌酸）恶二唑杂化结构配体在DNA促旋酶的结合口袋处表现出强烈的相互作用。
