Department of Biological Sciences, Sunway University, Petaling Jaya, Malaysia.
Department of Biochemistry, University of Malakand, Chakdara, Pakistan.
Sci Rep. 2021 Jul 5;11(1):13859. doi: 10.1038/s41598-021-92622-0.
The emergence and spread of antimicrobial resistance have been of serious concern to human health and the management of bacterial infectious diseases. Effective treatment of these diseases requires the development of novel therapeutics, preferably free of side effects. In this regard, natural products are frequently conceived to be potential alternative sources for novel antibacterial compounds. Herein, we have evaluated the antibacterial activity of the epicarp extracts of the Malaysian cultivar of yellow rambutan fruit (Nephelium lappaceum L.) against six pathogens namely, Bacillus subtilis, methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes, Pseudomonas aeruginosa, Klebsiella pneumoniae and Salmonella enterica. Among a series of solvent extracts, fractions of ethyl acetate and acetone have revealed significant activity towards all tested strains. Chemical profiling of these fractions, via HPLC, LC-MS and GC-MS, has generated a library of potentially bioactive compounds. Downstream virtual screening, pharmacological prediction, and receptor-ligand molecular dynamics simulation have eventually unveiled novel potential antibacterial compounds, which can be extracted for medicinal use. We report compounds like catechin, eplerenone and oritin-4-beta-ol to be computationally inhibiting the ATP-binding domain of the chaperone, DnaK of P. aeruginosa and MRSA. Thus, our work follows the objective to propose new antimicrobials capable of perforating the barrier of resistance posed by both the gram positives and the negatives.
抗菌药物耐药性的出现和传播一直严重威胁着人类健康和细菌性传染病的管理。有效治疗这些疾病需要开发新型治疗药物，最好没有副作用。在这方面，天然产物经常被认为是新型抗菌化合物的潜在替代来源。在此，我们评估了马来西亚黄荔枝果实（Nephelium lappaceum L.）外果皮提取物对六种病原体（枯草芽孢杆菌、耐甲氧西林金黄色葡萄球菌（MRSA）、化脓性链球菌、铜绿假单胞菌、肺炎克雷伯菌和肠炎沙门氏菌）的抗菌活性。在一系列溶剂提取物中，乙酸乙酯和丙酮部分对所有测试菌株均表现出显著活性。通过 HPLC、LC-MS 和 GC-MS 对这些部分进行化学分析，生成了一个潜在生物活性化合物库。下游虚拟筛选、药理学预测和受体-配体分子动力学模拟最终揭示了新型潜在抗菌化合物，可从中提取用于药用。我们报告了儿茶素、依普利酮和山奈酚-4-β-醇等化合物在计算上抑制了铜绿假单胞菌和 MRSA 的伴侣蛋白 DnaK 的 ATP 结合域。因此，我们的工作旨在提出能够穿透革兰氏阳性菌和革兰氏阴性菌耐药屏障的新型抗菌药物。
