Synthesis and Biological Evaluation of Purpurealidin E-Derived Marine Sponge Metabolites: Aplysamine-2, Aplyzanzine A, Suberedamines A and B

Kottakota, S.K; Evangelopoulos, D; Alnimr, A; Bhakta, S; McHugh, T.D; Gray, M; Groundwater, P.W; Marrs, E.C.L; Perry, J.D; Spilling, C.D; Harburn, J.J

Abstract

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. New value: 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.

Citation

Kottakota, S., Evangelopoulos, D., Alnimr, A., Bhakta, S., McHugh, T., Gray, M., …Harburn, J. (2012). Synthesis and Biological Evaluation of Purpurealidin E-Derived Marine Sponge Metabolites: Aplysamine-2, Aplyzanzine A, Suberedamines A and B. Journal of Natural Products, 75(6), 1090-1101. https://doi.org/10.1021/np300102z

• Journal Article Type: Article
• Publication Date: May 1, 2012
• Deposit Date: Oct 26, 2012
• Journal: Journal of natural products.
• Print ISSN: 0163-3864
• Electronic ISSN: 1520-6025
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 75
• Issue: 6
• Pages: 1090-1101
• DOI: https://doi.org/10.1021/np300102z
• Public URL: https://durham-repository.worktribe.com/output/1471554