title: Cytotoxic pyrroloiminoquinones from four new species of South African latrunculid sponges.
abstract: An examination of organic extracts of four new species of South African latrunculid sponges, Tsitsikamma pedunculata, T. favus, Latrunculia bellae, and Strongylodesma algoaensis, yielded 13 known and eight new pyrroloiminoquinone alkaloids, 3-dihydro-7,8-dehydrodiscorhabdin C (4), 14-bromo-3-dihydro-7,8-dehydrodiscorhabdin C (5), discorhabdin V (6), 14-bromo-1-hydroxydiscorhabdin V (7), tsitsikammamine A N-18 oxime (10), tsitsikammamine B N-18 oxime (11), 1-methoxydiscorhabdin D (12), and 1-aminodiscorhabdin D (13). Standard spectroscopic methods provided the structures of the pyrroloiminoquinone metabolites, while chiral GC-MS analysis of the acylated ozonolysis products of 21 confirmed the stereochemistry of the l-histidine residue in this compound. The anticancer activity of 20 pyrroloiminoquinone compounds was explored in the HCT-116 cancer cell line screen, and the DNA intercalation of the tsitsikammamines, together with their ability to cleave DNA through topoisomerase I inhibition, is discussed.
authors.affiliation: Department of Chemistry and Faculty of Pharmacy, Rhodes University, Grahamstown, South Africa.
authors.forename: Edith M
authors.initials: EM
authors.lastname: Antunes
authors.forename: Denzil R
authors.initials: DR
authors.lastname: Beukes
authors.forename: Michelle
authors.initials: M
authors.lastname: Kelly
authors.forename: Toufiek
authors.initials: T
authors.lastname: Samaai
authors.forename: Louis R
authors.initials: LR
authors.lastname: Barrows
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Marshall
authors.forename: Catherine
authors.initials: C
authors.lastname: Sincich
authors.forename: Michael T
authors.initials: MT
authors.lastname: Davies-Coleman
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D008401:Gas Chromatography-Mass Spectrometry; D045325:HCT116 Cells; D006639:Histidine / Q000737:chemistry; D006801:Humans; D015394:Molecular Structure; D011161:Porifera / Q000737:chemistry*; D013019:South Africa; D059004:Topoisomerase I Inhibitors
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D059004:Topoisomerase I Inhibitors; D006639:Histidine