Azadirone- and gedunin-type limonoids from Carapa procera seeds and their in vitro antimicrobial and antiproliferative activities.

The phytochemical study of the ethyl acetate extract of Carapa procera seeds led to the identification of two new limonoids, an azadirone-type limonoid, 6α,17β-dihydroxyazadiradione (1) and a gedunin-type limonoid, (-)-5-epi-5-hydroxy-7-deacetoxy-7-oxogedunin (2), as well as eleven known compounds, 6α-hydroxyazadiradione (3), 6-deoxydetigloylswietenin (4), mexicanolide (5), 7-deacetylgedunin (6), khayasin (7), 14,15-didehydroruageanin A (8), 17β-hydroxyazadiradione (9), xylomexicanolide A (10), swietmanin H (11), andirolide A (12), and krishnagranatin C (13). The structures were assigned based on comprehensive spectroscopic and X-ray crystallographic analyses in conjunction with TDDFT-ECD calculations. The relative configuration of the various stereocenters of selected molecules was established by ML-J-DP4. The antimicrobial and cytotoxic activities of the isolated compounds were evaluated against Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, and Mycobacterium marinum, in addition to breast cancer cell lines, and normal cells. In vitro cytotoxic activity was obtained, ranging from 0.758 to 0.035 μM, with the best activity obtained for (-)-5-epi-5-hydroxy-7-deacetoxy-7-oxogedunin (2) on the MCF-7 cell line. With an IC50 of 0.035 μM, this gedunin-type limonoid represents a promising candidate for further antiproliferative investigation. Moreover, 6-deoxydetigloylswietenin (4) exhibited moderate antimicrobial activity against M. marinum at a concentration of 100 μg/mL.