title: Synthesis and biological evaluation of purpurealidin E-derived marine sponge metabolites: aplysamine-2, aplyzanzine A, and suberedamines A and B.
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.
authors.affiliation: Sunderland Pharmacy School, Department of Pharmacy, Health and Well-Being, University of Sunderland, Wharncliffe Street, Sunderland, SR1 3SD, UK.
authors.forename: Suresh K
authors.initials: SK
authors.lastname: Kottakota
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Evangelopoulos
authors.forename: Amani
authors.initials: A
authors.lastname: Alnimr
authors.forename: Sanjib
authors.initials: S
authors.lastname: Bhakta
authors.forename: Timothy D
authors.initials: TD
authors.lastname: McHugh
authors.forename: Mark
authors.initials: M
authors.lastname: Gray
authors.forename: Paul W
authors.initials: PW
authors.lastname: Groundwater
authors.forename: Emma C L
authors.initials: EC
authors.lastname: Marrs
authors.forename: John D
authors.initials: JD
authors.lastname: Perry
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Spilling
authors.forename: J Jonathan
authors.initials: JJ
authors.lastname: Harburn
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D008386:Marine Biology; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D019906:Nuclear Magnetic Resonance, Biomolecular; D011161:Porifera / Q000737:chemistry*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; C574829:aplysamine-2; C433582:aplyzanzine A; C532295:purpurealidin E; C435811:suberedamine A; C435813:suberedamine B; D014443:Tyrosine; D015107:4-Butyrolactone