Department of Biotechnology, National Institute of Technology, Raipur, CG, INDIA.
Department of Biotechnology, National Institute of Technology, Raipur, CG, INDIA.
Int J Biol Macromol. 2018 Feb;107(Pt A):1212-1219. doi: 10.1016/j.ijbiomac.2017.09.102. Epub 2017 Sep 28.
In spite of therapeutic development against life threatening fungal pathogens like Candida albicans, the repertoire of effective antifungal drugs is lagging. The emergence and persistence of azole/echinocandin resistance and other cases of multi-drug resistance have led to the failure of the antifungal treatment regime. This troublesome scenario has steered a need for the development of novel leads. Computer aided in-silico drug design using virtual screening, molecular docking, drug likeness, absorption, distribution, metabolism, excretion, and toxicity analysis for the identification of lead compounds for further in-vitro analysis is a cost effective and time-saving strategy. The present study used these strategies to discover novel lead antifungal from the pool of second largest occurring natural compound lignin. After the virtual screening of lignin derivatives, Sodium lignosulfonate (LIG) was identified as the best lead for further analysis. After this vigorous in-silico analysis, LIG was then tested in-vitro against 5 different Candida species. MIC value of LIG against Candida spp. was found to be 64-128μg/ml. The study is revealing LIG as a potent and persuasive antifungal agent. In the race of Candida therapeutics, the revelation of the antifungal potential of such natural compounds might impact and diversify the discovery and development of novel antifungal agent.
尽管针对生命威胁性真菌病原体(如白色念珠菌)的治疗方法不断发展,但有效的抗真菌药物种类仍然有限。唑类/棘白菌素耐药性的出现和持续存在以及其他多药耐药性情况导致抗真菌治疗方案失败。这种麻烦的情况促使人们需要开发新的先导化合物。使用计算机辅助的基于虚拟筛选、分子对接、药物相似性、吸收、分布、代谢、排泄和毒性分析的计算机辅助药物设计,用于识别先导化合物,以便进一步进行体外分析,是一种具有成本效益和节省时间的策略。本研究使用这些策略从第二大天然化合物木质素库中发现了新型抗真菌先导化合物。在木质素衍生物的虚拟筛选后,确定木质素磺酸钠(LIG)是进一步分析的最佳先导化合物。在进行了这项深入的计算机模拟分析后,LIG 随后在体外对 5 种不同的念珠菌物种进行了测试。发现 LIG 对念珠菌属的 MIC 值为 64-128μg/ml。这项研究表明 LIG 是一种有效的抗真菌剂。在念珠菌治疗的竞赛中,揭示此类天然化合物的抗真菌潜力可能会影响和多样化新型抗真菌药物的发现和开发。