A secondary metabolite, 4,5-dibromopyrrole-2-carboxylic acid, from marine sponges of the genus Agelas alters cellular calcium signals

Abstract

A secondary metabolite from sponges of the genus Agelas, 4,5-dibromopyrrole-2-carboxylic acid, which is well known as feeding deterrent, was investigated for effects on the cellular calcium homeostasis in PC12 cells. 4,5-Dibromopyrrole-2-carboxylic acid did not change intracellular calcium levels if applied alone without cell depolarization. During depolarization of the cellular membrane using high potassium solution, a dose dependent reduction of intracellular calcium elevation was revealed utilizing Fura II as calcium indicator. Significant reduction was seen at concentrations higher than 30 M in a series of experiments, but in single experiments a concentration of 300 nM was still reversible effective. In the same concentration range, the onset of depolarization induced calcium elevations was significantly delayed by 4,5-dibromopyrrole-2-carboxylic acid. Dose dependent reduction and delay of depolarization evoked calcium elevations are probably due to a reduction of calcium entry via voltage operated calcium channels. One cellular mode of action of the feeding deterrent potential of 4,5-dibromopyrrole-2-carboxylic acid to fishes may be an interaction with the cellular calcium homeostasis of exposed cells.

In Vitro and In Vivo Assessment of the Efficacy of Bromoageliferin, an Alkaloid Isolated from the Sponge Agelas dilatata, against Pseudomonas aeruginosa

“…4-Bromo-1H-pyrrole-2-carboxylic acid (6) showed feeding deterrent activity (T. bifasciatum) [49] but no activity in reducing voltage dependent calcium elevation in PC12 cells [48], and also no cytotoxic (HL-60, K562, A549, and HCT-116 tumor cell lines) [32], no antitumoral activity against three human tumor cell lines (A549 lung cancer cells, HT29 colonic cancer cells and MDA-MB-231 breast cancer cells) [50] and no antimicrobial activity against C. albicans [32]. 4,5-Dibromopyrrole-2-carboxylic acid (7) displayed feeding deterrent activity (T. bifasciatum) [25,49,59], reduced voltage dependent calcium elevation in PC12 cells [48,60], enzyme inhibitory activity (PfFabI) [37], antiprotozoal activity (P. falciparum, T. brucei rhodesiense, T. cruzi and L. donovani) [37], immunosuppressive activity [61] and antifouling activity (B. amphitrite) [62]. However, compound 7 was not cytotoxic against rat skeletal myoblasts (L6 cells) [37], mouse lymphoma (L5178Y) [35], rat brain cancer (PC12) [35] or human cervix cancer cells (HeLa) [35] and did not display antitumoral activity against three human tumour cell lines (A549 lung cancer cells, HT29 colonic cancer cells and MDA-MB-231 breast cancer cells) [50], fungicidal activity (Ustilago violacea, Mycotypha microspora, Eurotium repens, Fusarium oxysporum [34], S. cerevisiea, C. cucumerinum, and C. herbarum [35], algicidal activity (Chlorella fusca) [34], activity in the protein kinase inhibition assays (cyclin-dependent kinase-1, cyclin-dependent kinase-5 and glycogen synthase kinase-3) [35], or inhibitory activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, acetylcholinesterase (AChE) [63] and protein tyrosine phosphatase 1B (PTP1B) [36].…”

A new species of Agelas from the Zanzibar Archipelago, western Indian Ocean (Porifera, Demospongiae)

“…Murray et al 2013) focuses on Agelas species as producers of interesting molecules e.g. Agelas clathrodes , Agelas linnaei , Agelas mauritiana , Agelas nakamurai , Agelas oroides , and Agelas sceptrum (Walker et al 1981, Fathi-Afshar et al 1989, Keifer et al 1991, Braekman et al 1992, Bernan et al 1993, König and Wright 1993, Chanas et al 1996, König et al 1998, Eder et al 1999, Assmann et al 2000, 2001, 2004, Fattorusso and Taglialatela-Scafati 2000, Assmann and Köck 2002, Fujita et al 2003, Bickmeyer et al 2004, 2005, 2008, Bickmeyer 2005, Costantino et al 2006, Meketa and Weinreb 2006, Ferretti 2006, Vik et al 2006, Ding et al 2007, Ferretti et al 2007, 2009, Vergne et al 2008, Hertiani et al 2010, Said et al 2010, Regalado et al 2011, Mordhorst et al 2015). In this scenario of intensive bioprospecting, research knowledge of systematics and taxonomy in depth is a key tool to identify and define the status of specimens/biomaterial to be processed.…”

Cytolytic and antinociceptive activities of starfish Protoreaster linckii (Blainvilli, 1893)

“…Marine organisms represent excellent source for bioactive compounds (Bickmeyer et al, 2005). Approximately 7000 marine natural products, 25% of which are from algae, 33% from sponges,18% from coelenterates, 24% from representatives of other invertebrate phyla such as ascidians, opisthobranches, mollusks, echinoderms and byrozoans (Anake, 2004).…”