Abstract：
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, 1H 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.
摘要：
设计并合成了一系列新型的喹诺酮取代的1,3,4-恶二唑衍生物4（a-l）。研究了目标化合物对革兰氏阳性（金黄色葡萄球菌，ATCC25923,粪肠球菌,ATCC29212）和革兰氏阴性细菌（大肠杆菌，ATCC25922,铜绿假单胞菌,ATCC27853）用于使用（白色念珠菌，ATCC10231）和作为COX-II抑制剂的抗炎活性，分别。在吡哌酸衍生物的C-6位引入1,3,4-恶二唑官能团。IR,1HNMR和质谱技术证实了合成衍生物的结构。喹诺酮（哌啶酸）-恶二唑杂合衍生物对细菌菌株有效。与环丙沙星（MIC16µg/mL）相比，正在考虑的化合物(4f，4h,和4k）对除粪肠球菌外的所有细菌菌株均显示出显着的抗菌活性，MIC为8µg/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没有很好的反应。化合物(4k)表现出对COX-II的高抑制%。化合物（4f，4h和4k）表现出与ARG57，ARG72，ARG78，LEU54和MET16靶残基的最高氢键相互作用，分别在DNA促旋酶活性口袋中的结合能为-8.4，-8.6和-8.5kcal/mol。与参考配体相比，甚至更好。在对接研究的基础上,喹诺酮（哌啶酸）恶二唑杂合结构配体在DNA促旋酶的结合袋中表现出强烈的相互作用。
