Abstract
The temperate marine sponge, Tsitsikamma favus, produces pyrroloiminoquinone alkaloids with potential as anticancer drug leads. We profiled the secondary metabolite reservoir of T. favus sponges using HR-ESI-LC-MS/MS-based molecular networking analysis followed by preparative purification efforts to map the diversity of new and known pyrroloiminoquinones and related compounds in extracts of seven specimens. Molecular taxonomic identification confirmed all sponges as T. favus and five specimens (chemotype I) were found to produce mainly discorhabdins and tsitsikammamines. Remarkably, however, two specimens (chemotype II) exhibited distinct morphological and chemical characteristics: the absence of discorhabdins, only trace levels of tsitsikammamines and, instead, an abundance of unbranched and halogenated makaluvamines. Targeted chromatographic isolation provided the new makaluvamine Q, the known makaluvamines A and I, tsitsikammamine B, 14-bromo-7,8-dehydro-3-dihydro-discorhabdin C, and the related pyrrolo-ortho-quinones makaluvamine O and makaluvone. Purified compounds displayed different activity profiles in assays for topoisomerase I inhibition, DNA intercalation and antimetabolic activity against human cell lines. This is the first report of makaluvamines from a Tsitsikamma sponge species, and the first description of distinct chemotypes within a species of the Latrunculiidae family. This study sheds new light on the putative pyrroloiminoquinone biosynthetic pathway of latrunculid sponges.
Highlights
Sponges of the family Latrunculiidae produce highly condensed and often brominated alkaloids such as makaluvamines, discorhabdins, and tsitsikammamines, collectively known as pyrroloiminoquinones [1,2]
More than fifty sponge specimens were collected by SCUBA or Remotely Operated Vehicle (ROV) from Evan’s Peak reef, Algoa Bay, South Africa, including TIC2015-027 in September 2015 and TIC2016-050A, TIC2016-050B, TIC2016-050C, TIC2016-050D, TIC2016-050AD, TIC2016-050AH, and TIC2016-050AW, from a single location, in March 2016
The associated microbiota of all sponge specimens was dominated by a conserved Betaproteobacterium Operational Taxonomic Unit (OTU) and a second, conserved Spirochetes OTU was present but in varying relative abundance (Figure 1E)
Summary
Sponges of the family Latrunculiidae produce highly condensed and often brominated alkaloids such as makaluvamines, discorhabdins, and tsitsikammamines, collectively known as pyrroloiminoquinones [1,2]. These compounds display a broad range of biological activities, including cytotoxic [3,4,5,6,7], antitumor [8], antimicrobial [9,10], antiplasmodial [11], and antioxidant activities [12], Mar. Drugs 2019, 17, 60; doi:10.3390/md17010060 www.mdpi.com/journal/marinedrugs. Pyrroloiminoquinones have attracted a surge of renewed interest as potential anticancer drug leads. Discorhabdins, and synthetic analogs have shown promising results in anticancer assays [3,4,15,16] and as inhibitors of the formation of the cancer-related HIF-1α/p300 enzyme complex [17]
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