Antibacterial activity of withanolides and their structure-activity relationship

[Display omitted] •Nine withanolides were isolated from Cuatresia Colombiana.•Several semisynthetic derivatives were obtained from withaferin A and Jaborosalactone 38.•The in vitro antibacterial activity of 25 natural compounds with different skeletons and 9 derivatives were evaluated.•The 1-oxo-2-ene-4β-OR-5β,6β-epoxy substitution pattern on rings A and B is critical for antibacterial activity. Two new withanolides, (17R,20S,22R)-4β-acetoxy-5β,6β-epoxy-19,27-dihydroxy-1-oxo-witha-2,24-dienolide (withalongolide A 4-acetate (5) and (17R,20S,22R)-5β,6β-epoxy-27-hydroxy-1,4-dioxo-witha-24-enolide (9), and seven known withanolides with normal structure (1–4, 6–8) were isolated from aerial parts of Cuatresia colombiana. Several semisynthetic derivatives were prepared from the natural metabolites withaferin A and jaborosalactone 38. The compounds were fully characterized by a combination of spectroscopic methods (1D and 2D NMR and MS). The compounds isolated from C. colombiana, sixteen withanolides previously isolated from different Solanaceae species with different skeletons and semisynthetic derivatives were evaluated for their antibacterial activity against a selected panel of Gram-positive and Gram-negative bacteria. According to the bioactivity against S. aureus and E. faecalis, the compounds evaluated were divided into three groups: compounds with high activity (MIC 0.063 mM), compounds with moderate activity (0.5 mM > MIC > 0.125 mM) and non-active compounds (MIC ≥1 mM); in addition, some structure-activity relationship keys could be inferred.