Rao Gollapalli Venkateswara, Babu Bollikolla Hari, Rao Allaka Tejeswara, Ranga Rao Vaddi Pandu, Basireddy Sravanthi, Ganivada Mutyalanaidu, Reddy Pindi Santhosh
Department of Chemistry, Acharya Nagarjuna University, Guntur, Andhra Pradesh-522004, India.
Chemical Research Department, APL Research Center-II, Aurobindo Pharma Ltd., Sangareddy, Telangana-502329, India.
Chem Biodivers. 2023 Apr;20(4):e202201259. doi: 10.1002/cbdv.202201259. Epub 2023 Apr 19.
Our current work is aimed at synthesizing novel substituted 1,2,4-triazolyl-fluoroquinolone analogs and study of their biological activity to find active promising molecules. The structural elucidation of the products was demonstrated by a variety of spectroscopic methods such as IR, H-NMR, C-NMR, mass and elemental analysis. The newly synthesized 1,2,4-triazole derivatives were tested in vitro for their ability to inhibit the growth of seven different microbes including S. epidermidis, S. pneumoniae, S. aureus, B. subtilis, K. pneumoniae, E. coli, and P. aeruginosa. Five FQ derivatives 5d, 5e, 5h, 5j, and 5b have demonstrated good antibacterial activity against S. pneumoniae with MICs ranging from 2.5-22.0 μg/mL, while 5c, 5g reported comparable activity against P. aeruginosa with respect to the standard drugs moxifloxacin and ciprofloxacin. The possible mechanism of antibacterial activity of fluoroquinolones was investigated via molecular docking by using DNA gyrase of S. pneumoniae (3RAE). The pefloxacin derivatives also tended a good antibacterial ability based on the results of the molecular docking, ligand 5h with good binding affinity (-9.92 Kcal/mol) and binding site interactions via ValA:86, SerA:79, TyrA:82, MetA:116, AspA:78, AlaA:63, ArgA:117, ProA:112, ProA:113, AlaA:115, AlaA:114. These scaffolds were further evaluated for their ADMET and physicochemical properties by using SwissADME, ADMETlab2.0 web server as a good oral bioavailability.
我们目前的工作旨在合成新型取代的1,2,4 - 三唑基 - 氟喹诺酮类似物，并研究其生物活性，以寻找有活性的潜在分子。通过多种光谱方法如红外光谱（IR）、氢核磁共振（¹H - NMR）、碳核磁共振（¹³C - NMR）、质谱和元素分析对产物进行结构解析。对新合成的1,2,4 - 三唑衍生物进行体外测试，以评估其抑制七种不同微生物生长的能力，这些微生物包括表皮葡萄球菌、肺炎链球菌、金黄色葡萄球菌、枯草芽孢杆菌、肺炎克雷伯菌、大肠杆菌和铜绿假单胞菌。五种氟喹诺酮衍生物5d、5e、5h、5j和5b对肺炎链球菌表现出良好的抗菌活性，其最低抑菌浓度（MIC）范围为2.5 - 22.0 μg/mL，而5c、5g对铜绿假单胞菌的活性与标准药物莫西沙星和环丙沙星相当。通过使用肺炎链球菌的DNA促旋酶（3RAE）进行分子对接，研究了氟喹诺酮抗菌活性的可能机制。基于分子对接结果，培氟沙星衍生物也具有良好的抗菌能力，配体5h具有良好的结合亲和力（-9.92 kcal/mol），并通过ValA:86、SerA:79、TyrA:82、MetA:116、AspA:78、AlaA:63、ArgA:117、ProA:112、ProA:113、AlaA:115、AlaA:114与结合位点相互作用。通过使用SwissADME、ADMETlab2.0网络服务器进一步评估这些支架的ADMET和理化性质，以确定其良好的口服生物利用度。
