title: Amantelides A and B, Polyhydroxylated Macrolides with Differential Broad-Spectrum Cytotoxicity from a Guamanian Marine Cyanobacterium.
abstract: Cytotoxicity-guided fractionation of a Guamanian cyanobacterial collection yielded the new compounds amantelides A (1) and B (2). These polyketides are characterized by a 40-membered macrolactone ring consisting of a 1,3-diol and contiguous 1,5-diol units and a tert-butyl substituent. Amantelide A (1) displayed potent cytotoxicity with submicromolar IC₅₀ against HT29 colorectal adenocarcinoma and HeLa cervical carcinoma cell lines. Acetylation of the hydroxy group at C-33 in 2 caused a close to 10-fold decrease in potency. Exhaustive acetylation of the hydroxy groups abrogated the antiproliferative activity of amantelide A (1) by 20-67-fold. Further bioactivity assessment of 1 against bacterial pathogens and marine fungi indicated a broad spectrum of bioactivity.
authors.affiliation: Marine Science Institute, University of the Philippines , Velasquez Street, UP Diliman, Quezon City 1101, Philippines.
authors.forename: Lilibeth A
authors.initials: LA
authors.lastname: Salvador-Reyes
authors.affiliation: Smithsonian Marine Station , 701 Seaway Drive, Fort Pierce, Florida 34949, United States.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Sneed
authors.affiliation: Smithsonian Marine Station , 701 Seaway Drive, Fort Pierce, Florida 34949, United States.
authors.forename: Valerie J
authors.initials: VJ
authors.lastname: Paul
authors.forename: Hendrik
authors.initials: H
authors.lastname: Luesch
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000458:Cyanobacteria / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D018942:Macrolides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D008386:Marine Biology; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011500:Protein Synthesis Inhibitors; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D000970:Antineoplastic Agents; D018942:Macrolides; D011500:Protein Synthesis Inhibitors; C000602737:amantelide A; C000602738:amantelide B