Cytotoxic pyrroloiminoquinones from four new species of South African latrunculid sponges.
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.
Antunes
Edith M
EM
Department of Chemistry and Faculty of Pharmacy, Rhodes University, Grahamstown, South Africa.
Beukes
Denzil R
DR
Kelly
Michelle
M
Samaai
Toufiek
T
Barrows
Louis R
LR
Marshall
Kathryn M
KM
Sincich
Catherine
C
Davies-Coleman
Michael T
MT
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
D000470:Alkaloids; D000970:Antineoplastic Agents; D059004:Topoisomerase I Inhibitors; D006639:Histidine