Department of Chemistry, Faculty of Engineering, Istanbul University-Cerrahpaşa, Avcilar, Istanbul, Turkey.
Chem Biodivers. 2024 Feb;21(2):e202301634. doi: 10.1002/cbdv.202301634. Epub 2024 Jan 19.
Clostridium perfringens (C. perfringens) is a bacterium that causes serious problems in humans and animals such as food poisoning, gas gangrene and infections. C. perfringens has three sialidases (NanH, NanI, NanJ) and inhibition of NanI constitutes an approach in the treatment of C. perfringens since NanI provides the carbohydrate source necessary for the growth of bacteria. In our study, the inhibition effect of some drugs belonging to different drug groups on NanI activity was investigated. Among these drugs, orlistat (0.21±0.05 μM) was determined to have a lower IC value than the positive control quercetin (15.58±1.59 μM). It was determined in vitro by spectrofluorometric method. Additionally, NanI molecular docking studies with orlistatand quercetin were performed using iGemdock, DockThor and SwissDock. Orlistat (-93.93, -8.649 and -10.03 kcal/mol, respectively) was found to have a higher binding affinity than quercetin (-92.68, -7.491 and -8.70 kcal/mol, respectively), and the results were in line with in vitro studies. The results may suggest that orlistat is a molecule with drug potential for C. perfringens because it inhibits the drug target NanI, and that the inhibition efficiency can be increased by studies with orlistat derivatives.
产气荚膜梭菌（C. perfringens）是一种能引起人类和动物严重问题的细菌，如食物中毒、气性坏疽和感染。产气荚膜梭菌有三种唾液酸酶（NanH、NanI、NanJ），抑制 NanI 是治疗产气荚膜梭菌的一种方法，因为 NanI 为细菌的生长提供了必要的碳水化合物来源。在我们的研究中，研究了属于不同药物类别的几种药物对 NanI 活性的抑制作用。在这些药物中，奥利司他（0.21±0.05 μM）的 IC 值低于阳性对照槲皮素（15.58±1.59 μM）。这是通过分光荧光法在体外确定的。此外，使用 iGemdock、DockThor 和 SwissDock 对奥利司他和槲皮素与 NanI 的分子对接进行了研究。奥利司他（分别为-93.93、-8.649 和-10.03 kcal/mol）的结合亲和力高于槲皮素（分别为-92.68、-7.491 和-8.70 kcal/mol），与体外研究结果一致。结果表明，奥利司他可能是一种具有产气荚膜梭菌药物潜力的分子，因为它抑制了药物靶标 NanI，并且通过奥利司他衍生物的研究可以提高抑制效率。
