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.

A revision of the genus Strongylodesma Lévi (Porifera: Demospongiae: Latrunculiidae) with descriptions of four new species

“…They were reassigned to Zyzzya fuliginosa by Van Soest et al (1996) (Poecilosclerida: Acarnidae) on the basis of their shared chemistry and morphological characteristics. Interestingly, makaluvic acids, damirones and makaluvamines, and discorhabdins (common to the Latrunculiidae) have now also been isolated from a South African latrunculid species Cyclacanthia bellae Samaai & Kelly, 2004. The discovery of a new pyrroloiminoquinone alkaloid (tsitsikammamine) that is biosynthetically intermediate to the makaluvamines of Zyzzya (Kelly, 2000;Samaai & Kelly, 2002;Antunes et al, 2005) and the discorhabdins of the Latrunculiidae, has also been isolated from Tsitsikamma favus Samaai & Kelly, 2002. Makaluvic acids, damirones, and makaluvamines, common to species of Zyzzya (Poecilosclerida: Acarnidae), and discorhabdins, common to species of Latrunculia, Strongylodesma, and Tsitsikamma (Poecilosclerida: Latrunculiidae), have been found in some species of Zyzzya and Cyclacanthia (Poecilosclerida: Latrunculiidae), indicating affinity between these genera.…”

Targeted Isolation of Tsitsikammamines from the Antarctic Deep-Sea Sponge Latrunculia biformis by Molecular Networking and Anticancer Activity

“…Discorhabdin pigments have been shown to be located in the outer layers of the Antarctic sponge species Latrunculia ( Latrunculia ) apicalis Ridley & Dendy, and linked to antifouling activity and the chemical defense of the sponge against the spongivorous sea star Perknstar fuscus [27]. Besides discorhabdins, the genus Latrunculia has repeatedly been reported to contain makaluvamines (pyrroloiminoquinones), epinardins (pyridopyrroloquinolines) and makaluvic acids (pyrroloquinoline) [28,29]. Tsitsikammamines that possess a non-brominated bis-pyrroloiminoquinone scaffold represent another group of pyrroloiminoquinone alkaloids that are closely related to discorhabdins.…”

“…Tsitsikammamines that possess a non-brominated bis-pyrroloiminoquinone scaffold represent another group of pyrroloiminoquinone alkaloids that are closely related to discorhabdins. This small alkaloid family has only been reported from the South African latrunculid sponge Tsitsikamma favus [28,30] and an Australian Zyzzya sp. [31].…”

α‐Bromoacrylamido N‐Substituted Isatin Derivatives as Potent Inducers of Apoptosis in Human Myeloid Leukemia Cells

“…[8] In light of this, several publications aimed to optimize the antitumor profile of isatin by synthesizing a range of analogues based on the isatin scaffold. [7,8] The pyrroloiminoquinone cytotoxic alkaloids discorhab-A C H T U N G T R E N N U N G din A [9] and discorhabdin G [10] are characterized by the presence of a a-bromoacryloyl alkylating moiety of low chemical reactivity, an unusual feature for cytotoxic compounds. In fact, a-bromoacrylic acid is not cytotoxic per se (the IC 50 value for L1210 cells is greater than 120 mm).…”