Bioorganic & Medicinal Chemistry ( IF 3.5 ) Pub Date : 2017-09-15 , DOI: 10.1016/j.bmc.2017.08.042 Cherupally Dayakar , Buddana Sudheer Kumar , Galande Sneha , Gudem Sagarika , Koneru Meghana , Sistla Ramakrishna , Reddy Shetty Prakasham , Bhimapaka China Raju
A series of novel pyrazolyl alcohols (5a-h), pyrazolyl azides (6a-h), and pyrazolyltriazoles (8a-h, 10a-p and 12a-l) were prepared and evaluated for their bioactivity (anti-bacterial and anti-inflammatory) profile. The compound 5c displayed the potent anti-bacterial activity against Micrococcus luteus (MIC 3.9 and MBC 7.81 µg/mL). In vitro anti-inflammatory activity data denoted that compound 8b is effective among the tested compounds against IL-6 (IC50 6.23 μM). Docking analysis of compounds 5f, 8a-b, 8e-f and 8h displayed high binding energies for the compounds 8a-b and 8h towards TNF-α dimer (2AZ5 protein) and IL-6 (1ALU protein). In vivo anti-inflammatory activity of compounds 8b and 8h with respect to LPS induced mice model indicated that compound 8h showed significant reduction in TNF-α.
中文翻译:
吡唑基三唑作为抗菌消炎剂的合成,药理活性和分子对接研究
制备了一系列新型的吡唑基醇(5a-h),吡唑基叠氮化物(6a-h)和吡唑基三唑(8a-h,10a-p和12a-1),并对其生物活性进行了评估(抗菌和消炎) ) 轮廓。化合物5c对黄褐微球菌(MIC 3.9和MBC 7.81 µg / mL)表现出有效的抗菌活性。体外抗炎活性数据表明,化合物8b在被测化合物中对IL-6(IC 50 6.23μM)有效。化合物5f,8a-b,8e的对接分析- ˚F和8H显示高结合能为化合物8A-B和8H朝TNF-α二聚体(2AZ5蛋白)和IL-6(1ALU蛋白)。相对于LPS诱导的小鼠模型,化合物8b和8h的体内抗炎活性表明化合物8h显示出TNF-α的显着降低。