Exploring in vitro and in silico potential inhibitory effects of eugenol and its analogues for broad range development of antibacterial drugs

The antibacterial potential of three herbal compounds, namely gymnemic acid, eugenol and shogaol, extracted from Gymnema sylvestre L. (gur mar), Syzygium aromaticum L. (clove), and Zingiber officinale L. (ginger), along with their silver nanoparticles (AgNps) was investigated against Staphylococcus aureus, Methicillin resistant Staphylococcus aureus, Escherichia coli, Salmonella enterica, and Klebsiella sp. Among all the herbal compounds and their AgNps, Eugenol showed highest antibacterial activity against E. coli (17 ± 0.5 mm), S. enterica (15 ± 0.4 mm), S. aureus (15 ± 0.28 mm) and MRSA (16 ± 0.28 mm) while Eugenol-AgNps remained more effective, with 16 ± 0.2 mm zone of inhibition for Klebsiella sp., as compared to pure eugenol. In broth dilution assay, eugenol (< 200 µl) and eugenol silver nanoparticles (< 12 mg) resulted in a significant decrease in bacterial growth, in all the tested bacteria. In silico screening of the selected herbal compounds against bacterial targets, including; 4CKL, 6J90, 7KHQ and 3DWK, was also performed. The in silico docking results also revealed eugenol as best the same on the basis of lowest binding energy (− 5.52 to − 7.08) and highest number of interactions (15 non-bonded contacts and 3 hydrogen bonds) with the target proteins. Tertiary screening of compounds was conducted on the basis of their oral bio-availability, LogP value and drug likeness properties. The drug likeness score of eugenol was − 0.74 i.e., in the range of non-drug like compounds, however, eugenol analogues EA3 (2-(4-hydroxy-3-methoxyphenyl) ethane-1,1-diol), and EA4 (2-(4-hydroxy-3-methoxyphenyl) ethane-1,1-diol) showed best drug likeness scores i.e., 0.26 and 0.39 respectively. Hence the hydroxylated analogues of eugenol can be the preferable drug candidates as broad spectrum antibacterial.