Pathophysiological effects of synthetic derivatives of polymeric alkylpyridinium salts from the marine sponge, Reniera sarai

Abstract

Polymeric 3-alkylpyridinium salts (poly-APS) are among the most studied natural bioactive compounds extracted from the marine sponge, Reniera sarai. They exhibit a wide range of biological activities, and the most prominent among them are the anti-acetylcholinesterase and membrane-damaging activity. Due to their membrane activity, sAPS can induce the lysis of various cells and cell lines and inhibit the growth of bacteria and fungi. Because of their bioactivity, poly-APS are possible candidates for use in the fields of medicine, pharmacy and industry. Due to the small amounts of naturally occurring poly-APS, methods for the synthesis of analogues have been developed. They differ in chemical properties, such as the degree of polymerization, the length of the alkyl chains (from three to 12 carbon atoms) and in the counter ions present in their structures. Such structurally defined analogues with different chemical properties and degrees of polymerization possess different levels of biological activity. We review the current knowledge of the biological activity and toxicity of synthetic poly-APS analogues, with particular emphasis on the mechanisms of their physiological and pharmacological effects and, in particular, the mechanisms of toxicity of two analogues, APS12-2 and APS3, in vivo and in vitro.

Figure 1

Synthesis of poly-(1,3-alkylpyridinium) salts. Reagents and conditions: for R = alkyl chain: (i) HBr, toluene, reflux overnight followed by neutralization to yield products with X = Br; thionyl chloride, dichloromethane, room temperature to yield products with X = Cl; (ii) reflux in acetonitrile or methanol (in the presence of a small amount of KCl for monomeric chloride), followed by microwave irradiation at 130 °C for the time length stated for each compound under the experimental section. Adapted from Zovko et al. [29], with permission from © 2012 Elsevier Ltd.