RESUMO
The first total synthesis of the marine natural products Psammaplin C and Tokaradine A is described. Benzylidene rhodanines were utilized as versatile intermediates toward the synthesis of seven brominated marine sponge metabolites through the optimization of protection group strategies. Spermatinamine demonstrated good inhibition of all cancer cell lines tested, in particular the leukemia K562 and colon cancer HT29 cell lines.
Assuntos
Compostos de Benzilideno/síntese química , Hidrocarbonetos Bromados/síntese química , Rodanina/análogos & derivados , Sulfonas/síntese química , Animais , Compostos de Benzilideno/química , Compostos de Benzilideno/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Células HT29 , Humanos , Hidrocarbonetos Bromados/química , Hidrocarbonetos Bromados/farmacologia , Biologia Marinha , Estrutura Molecular , Poríferos/química , Rodanina/síntese química , Rodanina/química , Rodanina/farmacologia , Espermina/análogos & derivados , Espermina/farmacologia , Sulfonas/química , Sulfonas/farmacologia , Tirosina/análogos & derivados , Tirosina/farmacologiaRESUMO
Five purpurealidin-derived marine secondary sponge metabolies have been synthesized through the carbodiimide coupling of an appropriate bromotyrosine unit. The structure elucidations have been confirmed through direct comparison with spectroscopic data of isolated natural products. Aplyzanzine A has been shown to be the most active product against a broad bacterial and fungal screen, demonstrating MIC values 2 to 4 times lower than the other metabolites in this study. Compounds 2, 3, 4a, and 5-7 exhibit a modest inhibition against slow growing mycobacteria (MIC 25-50 µg/mL), including Mycobacterium tuberculosis. iso-Anomoian A and suberedamine B showed antitumor activity in the NCI-DTP60 cell line screen at single-digit micromolar concentrations, with iso-anomoian A inhibiting 53 cell lines. These molecules present novel scaffolds for further optimization.
