Department of Chemistry, Tripura University, Suryamaninagar, Tripura, 799022, India.
Department of Molecular Biology & Bioinformatics, Tripura University, Suryamaninagar, Tripura, 799022, India.
World J Microbiol Biotechnol. 2018 Nov 8;34(11):170. doi: 10.1007/s11274-018-2545-1.
Coumarin is an important heterocyclic molecular framework of bioactive molecules against broad spectrum pathological manifestations. In the present study 18 new coumarin derivatives (CDs) were synthesized and characterized for antibiofilm activity against two model bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa. It was observed that all the CDs executed significant effect in moderating activities against both planktonic and biofilm forms of these selected bacteria. Hence, to interpret the underlying probable reason of such antibiofilm effect, in-silico binding study of CDs with biofilm and motility associated proteins of these organisms were performed. All CDs have shown their propensity for occupying the native substrate binding pocket of each protein with moderate to strong binding affinities. One of the CDs such as CAMN1 showed highest binding affinity with these proteins. Interestingly, the findings of in-silico studies coincides the experimental results of antibiofilm and motility affect of CDs against both S. aureus and P. aeruginosa. Moreover, in-silico studies suggested that the antibiofilm activity of test CDs may be due to the interference of biofilm and motility associated proteins of the selected model organisms (PilT from P. aeruginosa and TarK, TarO from S. aureus). The detailed synthesis, characterization, methodology and results of biological screening along with computational studies have been reported. This study could be of greater interest in the context of the development of new anti-bacterial agent in the future.
香豆素是一类具有广泛生物活性的重要杂环分子骨架，可用于治疗多种疾病。本研究合成了 18 种新型香豆素衍生物（CDs），并对其抗生物膜活性进行了评价，所选模型菌为金黄色葡萄球菌和铜绿假单胞菌。结果表明，所有 CDs 均能显著抑制这两种细菌的浮游态和生物被膜态生长。为了探究 CD 产生抗生物膜作用的可能机制，我们对其与两种受试菌生物被膜和运动相关蛋白进行了计算机对接研究。结果显示，所有 CDs 均能与这些蛋白的天然底物结合口袋结合，且结合亲和力为中等至较强。其中，化合物 CAMN1 与这些蛋白的结合亲和力最强。有趣的是，计算机对接研究的结果与 CD 对两种受试菌的抗生物膜和运动抑制活性的实验结果相吻合。此外，计算机对接研究提示，CD 的抗生物膜活性可能是由于其对所选模式菌生物被膜和运动相关蛋白（铜绿假单胞菌的 PilT 和金黄色葡萄球菌的 TarK、TarO）的干扰所致。本研究详细报道了化合物的合成、结构鉴定、生物学筛选方法和结果，以及计算机模拟研究。这一研究可能为未来新型抗菌药物的开发提供新的思路。
