Department of Chemistry, Faculty of Mathematics and Natural Science, Universitas Padjadjaran, Sumedang, Indonesia.
Department of Pediatric Dentistry, Faculty of Dentistry, Universitas Padjadjaran, Bandung, Indonesia.
Comb Chem High Throughput Screen. 2022;25(9):1488-1497. doi: 10.2174/1386207324666210707104440.
Streptococcus sanguinis can contribute to tooth demineralization, which can lead to dental caries. Antibiotics used indefinitely to treat dental caries can lead to bacterial resistance. Discovering new antibacterial agents from natural products, like Ocimum basilicum, will help combat antibiotic resistance. In silico analysis (molecular docking) can help determine the lead compound by studying the molecular interaction between the drug and the target receptor (MurA enzyme and DNA gyrase). It is a potential candidate for antibacterial drug development.
The research objective is to isolate the secondary metabolite of O. basilicum extract that exhibits activity against S. sanguinis through in vitro and in silico analysis.
n-Hexane extract of O. basilicum was purified by combining column chromatography with bioactivity-guided fractionation. The in vitro antibacterial activity against S. sanguinis was determined using the disc diffusion and microdilution method, while molecular docking simulation of nevadensin (1) with MurA enzyme and DNA gyrase was performed by using PyRx 0.8 program.
Nevadensin from O. basilicum was successfully isolated and characterized by spectroscopic methods. This compound showed antibacterial activity against S. sanguinis with MIC and MBC values of 3750 and 15000 μg/mL, respectively. In silico analysis showed that the binding affinity to MurA was -8.5 Kcal/mol, and the binding affinity to DNA gyrase was -6.7 Kcal/mol. The binding of nevadensin-MurA is greater than fosfomycin-MurA. Otherwise, Nevadensin-DNA gyrase has a weaker binding affinity than fluoroquinolone-DNA gyrase and chlorhexidine-DNA gyrase.
Nevadensin showed potential as a new natural antibacterial agent by inhibiting the MurA enzyme rather than DNA gyrase.
血链球菌可导致牙齿脱矿，进而引发龋齿。为治疗龋齿而无限期使用抗生素会导致细菌耐药。从天然产物（如罗勒）中发现新的抗菌剂有助于对抗抗生素耐药性。计算机模拟分析（分子对接）可以通过研究药物与靶受体（MurA 酶和 DNA 回旋酶）之间的分子相互作用，帮助确定先导化合物。它是一种有潜力的抗菌药物开发候选物。
本研究旨在通过体外和计算机模拟分析，从罗勒提取物中分离出对血链球菌具有活性的次生代谢产物。
采用柱色谱结合生物活性导向分离法对罗勒 n-己烷提取物进行纯化。采用纸片扩散法和微量稀释法测定提取物对血链球菌的体外抑菌活性，采用 PyRx 0.8 程序进行新穿心莲内酯（1）与 MurA 酶和 DNA 回旋酶的分子对接模拟。
成功分离并通过光谱方法对罗勒中的新穿心莲内酯进行了表征。该化合物对血链球菌具有抑菌活性，MIC 和 MBC 值分别为 3750 和 15000μg/mL。计算机模拟分析表明，该化合物与 MurA 的结合亲和力为-8.5 Kcal/mol，与 DNA 回旋酶的结合亲和力为-6.7 Kcal/mol。新穿心莲内酯与 MurA 的结合亲和力大于磷霉素。此外，新穿心莲内酯-DNA 回旋酶的结合亲和力弱于氟喹诺酮-DNA 回旋酶和洗必泰-DNA 回旋酶。
新穿心莲内酯通过抑制 MurA 酶而不是 DNA 回旋酶，显示出作为新型天然抗菌剂的潜力。
