Oleanolic acid: an antimycobacterial component of Syzygium aromaticum L. and inhibitor of efflux mediated drug resistance.

Oleanolic acid (OA) was isolated from Syzygium aromaticum L. buds, and structurally characterised using different spectroscopic techniques; MS, IR,1H/13C-NMR and 2D NMR experiments. The antimycobacterial activity according to a resazurin microtiter assay (REMA) showed important inhibitory effect of OA on the virulent H37Rv strain, with the lowest minimum concentration of 50 µg/mL, compared to other fractions. Molecular docking of OA with BacA drug efflux pump resulted in good binding affinity of hydrophobic interaction type. Therefore, OA could contribute to the antimycobacterial action of clove buds, and has potential as an efflux pump inhibitor. Further studies are required on its use to combat multidrug resistant strains.

Clove Buds Volatile Compounds: Inhibitory Activity on Mycobacterium Growth and Molecular Docking on Mmr Efflux Pump Drug Resistance.

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 ß-caryophyllene as common major compounds. According to Resazurin microtiter assay (REMA), Mycobacterium tuberculosis H37 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.

Crystal structure and Hirshfeld surface analysis of 4-allyl-2-meth-oxy-6-nitro-phenol.

The asymmetric unit of the title compound, C10H11NO4, which was synthesized via nitration reaction of eugenol (4-allyl-2-meth-oxy-phenol) with a mixture of nitric acid and sulfuric acid, consists of three independent mol-ecules of similar geometry. Each mol-ecule displays an intra-molecular hydrogen bond involving the hydroxide and the nitro group forming an S(6) motif. The crystal cohesion is ensured by inter-molecular C-H⋯O hydrogen bonds in addition to π-π stacking inter-actions between the aromatic rings [centroid-centroid distances = 3.6583 (17)-4.0624 (16) Å]. The Hirshfeld surface analysis and the two-dimensional fingerprint plots show that H⋯H (39.6%), O⋯H/H⋯O (37.7%), C⋯H/H⋯C (12.5%) and C⋯C (4%) are the most important contributors towards the crystal packing.