Semi-síntese e avaliação da atividade citotóxica e antimicrobiana de derivados da annonalida, diterpeno isolado de humirianthera ampla

Abstract

The pimarane diterpeno annonalida (11) was isolated from roots of Humirianthera ampla and chemically converted into derivatives ANN-ACET (79), ANN-PROP (80), ANNHEXA (81), ANN-DECA (82) e ANN-Cl (83). Among them, compounds 80-83 are new in the literature. Natural products 16 and 17, and the semisynthetic derivatives 11 were tested in cytotoxicity assays against the human tumor cell lines OVCAR-8 (ovarian), HCT-116 (colon), HL-60 (leukemia) and SF-295 (glioblastoma), and antimicrobial activity against strains of Escherichia coli (ATCC 10536), Pseudomonas aeruginosa (ATCC 1026), Staphylococcus aureus (ATCC 6538), Bacillus subtilis (ATCC 6633) and Candida albicans (ATCC 10231). Annonalida (11) showed high cytotoxicity against SF-295 (IC50 0.09 mg/mL), and compound 80 was more active than 11 against two of the four strains tested (0.32 µg/mL against HL-60 and 2.56 µg/mL against OVCAR-8). In the antimicrobial assay, all compounds showed no zone of inhibition against bacteria, and FICI=1.5 (no synergism with fluconazole) against resistant fungi.