Synthesis, antibacterial activity and molecular docking studies of foetidumin A derivatives

A chemical reinvestigation of the n-hexane soluble portion of the methanolic extract obtained from the leaves of Helichrysum foetidum Moench. afforded five known secondary metabolites. Foetidumin A (1), was subjected to chemical derivatizations, yielding three new semisynthetic derivative namely, (4 R) ent-3-keto-19-norbeyer-15-ene (1a), ent-3β-acetoxy-15R,16S-epoxybeyeran-19-oic acid (1b), and ent-3R,15S,16S-trihydroxybeyeran-19-oic acid (1d), along with a known ent-3β-hydroxy-15-beyeren-19-oic acid (1c). Their structures were assigned on the basis of their spectrometric (HRESIMS) and spectroscopic (1D and 2D) NMR data. Foetidumin A (1) exhibited significant activities against Pseudomonas aeruginosa (MIC = 4.7 µg/mL), Mycobacterium smegmatis and Bacillus subtilis (MIC = 9.4 µg/mL), and a moderate activity against Escherichia coli (MIC = 18.8 µg/mL), while compounds 1a and 1b exhibited moderate activities against P. aeruginosa (MIC = 75 and 37.5 µg/mL, respectively). The in silico molecular docking analysis indicated that progressive structural modification away from the reference scaffold disrupts productive binding within the 4OAD (P. aeruginosa) active site.