Comparison of Fascaplysin and Related Alkaloids:  A Study of Structures, Cytotoxicities, and Sources

• Published in: Journal of natural products (Washington, D.C.) Vol. 67; no. 5; pp. 783 - 792
• Main Authors: Segraves, Nathaniel L, Robinson, Sarah J, Garcia, Daniel, Said, Sadri A, Fu, Xiong, Schmitz, Francis J, Pietraszkiewicz, Halina, Valeriote, Frederick A, Crews, Phillip
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.05.2004; Amer Chemical Soc; American Society of Pharmacognosy
• Subjects: Alkaloids - chemistry; Alkaloids - isolation & purification; Alkaloids - pharmacology; Animals; Biological and medical sciences; Chemistry, Medicinal; Drug Screening Assays, Antitumor; Fiji; General pharmacology; Humans; Hydrocarbons, Brominated - chemistry; Hydrocarbons, Brominated - isolation & purification; Hydrocarbons, Brominated - pharmacology; Indoles - chemistry; Indoles - isolation & purification; Indoles - pharmacology; Indonesia; Inhibitory Concentration 50; Life Sciences & Biomedicine; Medical sciences; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Pharmacognosy. Homeopathy. Health food; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Plant Sciences; Porifera - chemistry; Science & Technology; Tumor Cells, Cultured; Urochordata - chemistry; Fiji; Asia; Melanesia; Oceania; Indonesia; PROTEIN-KINASE-C; MINOR METABOLITES; BIOSYNTHETIC GENE-CLUSTER; STAUROSPORINE DERIVATIVES; APLYSINOPSIN; ASCIDIAN EUDISTOMA-TOEALENSIS; SCLERACTINIAN CORAL; BETA-CARBOLINE; PHASE-I; MARINE; Antineoplastic agent; Pentacyclic compound; Angular nitrogen heterocycle; Nitrogen heterocycle; Lactam; Cytotoxicity; Urochordata; Benzoic acid derivatives; Marine environment; Ester; Alkaloid; Carboxylic acid; Bromine Organic compounds; Aromatic compound; Tumor cell; Human; Pharmacognosy; Rodentia; Animal origin; Prochordata; Tricyclic compound; In vitro; Biological activity; Vertebrata; Mammalia; Cell line; Mouse; Porifera; Animal; Isolation; Invertebrata; Structural analysis
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np049935+

The fascaplysin class of compounds have been further investigated from six organisms consisting of four sponge collections (Fascaplysinopsis reticulata) and two tunicate collections (Didemnum sp.). This work is an extension of an earlier communication and reports the isolation of 12 new fascaplysin derivatives:  10-bromofascaplysin (7), 3,10-dibromofascaplysin (8), homofascaplysate A (9), homofascaplysin B-1 (11), 3-bromohomofascaplysins B (12), B-1 (13), and C (15), 7,14-dibromoreticulatine (17), reticulatol (20), 14-bromoreticulatol (21), and 3-bromosecofascaplysins A (22) and B (23), along with known compounds:  fascaplysin (1), reticulatine (4), 3-bromofascaplysin (6), and homofascaplysin C (14). Selected compounds were screened in a cell-based cytotoxicity assay with compounds 1, 6, and fascaplysin A (24) also screened in the NCI 60 cell line panel. A biogenetic pathway for the brominated fascaplysins and brominated related alkaloids is proposed and discussed.