Disturbance of voltage-induced cellular calcium entry by marine dimeric and tetrameric pyrrole–imidazole alkaloids

Abstract

Twelve brominated pyrrole-imidazole alkaloids from the Caribbean sponges Stylissa caribica and Agelas wiedenmayeri were tested for interactions with cellular calcium homeostasis using PC12 cells. Massadine (half maximal concentration: 5.3270.007 mM), stylissadines A (4.4871.1 mM) and B (4.671.6 mM) as well as tetrabromostyloguanidine (15.670.004 mM) reduced voltage-dependent calcium entry in PC12 cells as measured with Fura II as calcium indicator. Dibromopalau 0 amine and mauritiamine reduced voltage-dependent calcium entry but no half maximal concentration can be calculated from our results. Monomeric brominated pyrrole alkaloids such as stevensine, cyclooroidin, oxocyclostylidol, 4-bromopyrrole-2-carboxy-N(e)-lysine, and 4-bromopyrrole-2-carboxyarginine showed no or only minor effects. Ageladine A itself showed fluorescence in a similar range as Fura II and therefore no data are reported here. Based on the results a structure-activity relationship could be established. Absolutely necessary for an activity seem to be a lipophilic (brominated side chain) and a hydrophilic (amino-imidazole core) substructure. The combination of these substructures may be on one hand responsible for the membrane solubility (dibromopyrrole moieties) and on the other hand for the interaction with the hydrophilic area of the calcium channel (amino-imidazole moieties) to accomplish the alkaloids neurotoxic potential. r

The Alkaloid Ageladine A, Originally Isolated from Marine Sponges, Used for pH-Sensitive Imaging of Transparent Marine Animals

“…Other brominated pyrrole-imidazole alkaloid compounds than Ageladine A have been shown to interact with the cellular calcium signaling [28,29] and are bad-tasting substances, which prevents common reef fishes feeding on sponges [3,30]. The most effective alkaloids in both cases are the dimers of pyrrole-imidazoles.…”

Tracking of fast moving neuronal vesicles with ageladine A

“…For example, sponges are well known to produce a large number of bioactive compounds such as brominated pyrrole imidazoles as feeding deterrents against predatory fishes [6,7,8]. Some brominated pyrrole imidazole alklaloids are known to be cytotoxic [9] and to interact with ion channels and be involved in cellular signalling in mammalian and invertebrate cells [10,11,12].…”

Marine Invertebrates: Sponges

“…142 Palau'amine (96) is a cytotoxic and immunosuppressive compound originally isolated from the Palauan Stylotella agminata. 151 Stellettamide A (99), an unusual indolizidine alkaloid originally isolated from Stelletta sp. [144][145][146] The detailed overview of the structural revision was documented by Köck et al 147 Ageladine A (98) is a matrix metalloproteinase (MMP)-inhibiting fluorescent alkaloid isolated from the sponge Agelas nakamurai.…”