Biological Evaluation and Molecular Docking Study of Euparin and Its Maleic Anhydride and Semicarbazide Derivatives

Euparin (1) as a natural product was derivatized by maleic anhydride (2), semicarbazide (3), phenylacetic acid (4 and 5), and thiosemicarbazide (6) and their activities were evaluated in silico by molecular docking studies to investigate the binding affinities and interaction modes between the samples and N-myristoyltransferase enzyme. Among the tested samples (1-6), compounds 1-3 showed significant hydrophobic and hydrogen bonding interactions with the important residues at the active site of the receptor. Therefore, the biological properties of compounds 1-3 were investigated in this work. The antifungal activity of compounds 1-3 was tested against Candida albicans. Amongst them, euparin 1 with minimum inhibitory concentration (MIC) of 7.81 mu g/mL and minimum fungicidal concentration (MFC) of 15.62 mu g/mL exhibited the highest antifungal activity. Furthermore, antibacterial activities were studied against two Gram-positive (Staphylococcus aureus and Bacillus subtilis), and two Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria, the highest zone of growth on B. subtilis for compound 3 was 13.5 +/- 0.7 mm, while for compound 2, the zone of growth inhibition against B. subtilis and S. aureus was 10.0 +/- 1.4 and 9.5 +/- 0.70 mm, respectively. Finally, the anticancer effects of 1- 3 were examined using MTT assay against MDA-MB-231 and A-549 cell lines. Compound 2 displayed cytotoxicity on MDA-MB-231 cell line with IC50 of 166 mu g/mL.

Automated summary

In this study, the binding affinities and interaction modes between Euparin derivatives and N-myristoyltransferase enzyme were evaluated through molecular docking studies. Compounds 1-3 exhibited significant hydrophobic and hydrogen bonding interactions with important residues at the active site of the receptor. Among them, compound 1 showed the highest antifungal activity, compound 2 displayed cytotoxicity against a cancer cell line, and compound 3 exhibited strong growth inhibition against a bacterial strain.