Antihemolytic and Thrombolytic Potential of Ocimum basilicum Seed Extract, Bioactive Compounds, and Docking With VanA Ligase in Vancomycin-Resistant Staphylococci

罗勒籽提取物、生物活性化合物及其与耐万古霉素葡萄球菌VanA连接酶的结合的抗溶血和溶栓潜力

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Abstract

Ocimum basilicum is an important alternative source to explore diverse anti-infective compounds. In the present study, aqueous seed extract of O. basilicum was used to identify bioactive compounds with antihemolytic, thrombolytic, antivancomycin-resistant Staphylococcus aureus and antivancomycin-resistant S. epidermidis activity. Anti-VRSA and anti-VRSE activity of O. basilicum seed aqueous extract was evaluated by the well diffusion assay. Hemolytic and thrombolytic activities were performed using a 96-well plate. Phytochemical identification was done by GC-MS. ADMET and docking analyses with VanA ligase of VRSA and VRSE were also performed. The aqueous extract showed antibacterial activity against VRSA (12 ± 0.35 mm) and VRSE (13 ± 0.11 mm) isolates. The O. basilicum showed significantly less hemolysis (3.7 ± 0.24%, p < 0.00001) of red blood cells, reflecting low cytotoxicity as compared to the control (98 ± 0.44%). The O. basilicum seed extract exhibited significant thrombolytic activity (4.33 ± 0.2%, p < 0.000429) as compared to the negative control (2 ± 0.34%). Among 23 identified compounds on GC-MS, eight were reported for the first time in O. basilicum aqueous seed extract and processed for molecular docking. After favorable water solubility, pharmacokinetics, medicinal chemistry, and drug likeness, only two compounds, d-glucopyranoside, 2,3,4,6-di-O-(ethylboranediyl)-1-O-methyl and 4(3,4-dihydroxy-2-oxo-butylamino) benzonitrile, were processed for molecular docking. The first one formed three hydrogen bonds with Leu-259, Ser-127, and His-49 residues of the VanA ligase. The second one formed two hydrogen bonds with Ser-161 and Val-160 residues of the VanA ligase. d-Glucopyranoside, 2,3,4,6-di-O-(ethylboranediyl)-1-O-methyl and 4(3,4-dihydroxy-2-oxo-butylamino) benzonitrile. The O. basilicum seed extract has potential bioactivity, and the identified compounds are novel putative VanA ligase inhibitors. Further characterization of the bioactive compounds would help to explore therapeutic targets against VRSA and VRSE.

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