Citrinadin A derivatives from Penicillium citrinum, an endophyte from the marine red alga Dichotomaria marginata

Fungi isolated from marine organisms have been shown to produce interesting secondary metabolites which may represent an important source for bioprospection. Quinolizidine alkaloids isolated from Penicillium citrinum present a unique spiroindolinone moiety fused to a quinolizidine bicyclic unit forming a pentacyclic structure. The fungal strain was isolated from Dichotomaria marginata, collected from Brazil SE coast, and was grown in sterile rice solid media, which was then extracted with MeOH. CC of the MeCN fr. over Sephadex LH-20 afforded four quinolizidine alkaloids (1 – 4) after purification by HPLC-DAD. Their identification was based on spectral analyses, in addition to comparison with literature data and Antimarin® databank. UV data indicated the presence of similar chromophores with λmax 335nm, associated to the indolinone moiety. HRMS analyses of the isolated compounds indicated their molecular formula and 1D and 2D NMR data led to the identification of 1 – 4 as citrinadin A, citrinadin B, 18-dehydroxy-citrinadin B and chrysogenamide. Such compounds exhibited cytotoxicity against murine leukemia and human epidermoid carcinoma KB cells in previous studies, and thus our results may represent an important contribution for the exploration of marine biodiversity.