El Ghallab Yassine, Eddine Jamal Jamal, Aainouss Achraf, El Messaoudi My Driss, Dakir Mohamed, Derfoufi Sanae
Laboratory of Drugs Sciences, Biomedical Research and Biotechnology, Faculty of Medicine and Pharmacy, Hassan II University of Casablanca, B.P. 9154, Casablanca, 20250, Morocco.
Laboratory of Organic Synthesis, Extraction and Valorization, Department of Chemistry, Faculty of Sciences Ain Chock, Hassan II University of Casablanca, B.P. 5366, Casablanca, 20000, Morocco.
Chem Biodivers. 2023 Oct;20(10):e202300895. doi: 10.1002/cbdv.202300895. Epub 2023 Oct 2.
Syzygium aromaticum is used in traditional and modern medicine for its various and outstanding pharmacological properties. Here, we studied the chemical composition of hexane extract and non-polar fractions (NPF) obtained from the maceration and fractionation of clove buds, in order to evaluate their in vitro antimycobacterial activity, as well as their contribution against efflux pump (EP) resistance through molecular docking experiments. The gas chromatography-mass spectrometry (GC-MS) analysis of the volatile profiles revealed the presence of eugenol, followed by eugenyl acetate, and β-caryophyllene as common major compounds. According to Resazurin microtiter assay (REMA), Mycobacterium tuberculosis H Rv strain was sensitive to all volatile samples at concentration range between 10 and 100 μg/mL. The NPF of ethanol extract was the best inhibitor with a MIC=10 μg/mL. The in silico study revealed a strong binding affinity between eugenol and Mmr EP protein (-8.1 Kcal/mol), involving two binding modes of hydrogen bond and π-alkyl interactions. The non-polarity character of clove volatile constituents, and their potential additive or synergistic effects could be responsible for the antimycobacterial activity. In addition, these findings suggest the benefic effect of eugenol in the management of mycobacterium drug resistance, whether as potential inhibitor of Mmr drug EP, or modulator during combination therapy.
丁香因其多样且出色的药理特性而被应用于传统医学和现代医学。在此，我们研究了从丁香花蕾浸渍和分馏得到的己烷提取物和非极性馏分（NPF）的化学成分，以评估它们的体外抗分枝杆菌活性，以及通过分子对接实验评估它们对耐药泵（EP）耐药性的作用。挥发性成分的气相色谱 - 质谱（GC - MS）分析显示，丁香酚、乙酸丁香酚酯和β - 石竹烯是常见的主要化合物。根据刃天青微量滴定法（REMA），结核分枝杆菌H37Rv菌株对浓度在10至100μg/mL之间的所有挥发性样品敏感。乙醇提取物的NPF是最佳抑制剂，MIC = 10μg/mL。计算机模拟研究表明丁香酚与Mmr EP蛋白之间具有很强的结合亲和力（-8.1千卡/摩尔），涉及氢键和π - 烷基相互作用的两种结合模式。丁香挥发性成分的非极性特征及其潜在的相加或协同作用可能是其抗分枝杆菌活性的原因。此外，这些发现表明丁香酚在治疗分枝杆菌耐药性方面具有有益作用，无论是作为Mmr药物EP的潜在抑制剂，还是联合治疗期间的调节剂。
