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.

Gracilin A Derivatives Target Early Events in Alzheimer’s Disease: in Vitro Effects on Neuroinflammation and Oxidative Stress

“…These sessile organisms from the phylum Porifera produce several secondary metabolites with defensive functions against pathogens, predators, or for space competition. Many of these bioactive molecules have been used as drug leads , and some synthetic derivatives have been approved for clinical use or have progressed to Phase II/III clinical trials …”

Natural polymeric 3-alkylpyridinium salt affects vertebrate skeletal muscle contractility by preferentially blocking neuromuscular transmission

“…Its application in medicine led to the synthesis of a series of synthetic analogs with different degrees of polymerization and different lengths of alkyl chains (Houssen et al, 2010). Recently, the effects of some of these synthetic analogs due to their AChE inhibitory potency were studied on the skeletal neuromuscular transmission (reviewed in Grandic and Frangez, 2014). Experiments on skeletal neuromuscular preparations revealed that APS12-2, a non-competitive AChE inhibitor which was previously shown to be selectively cytotoxic toward NSLC cells in vitro, is a potent antagonist of skeletal muscle nAChRs (Grandic et al, 2012).…”

“…Synthetic analogs of Poly-3-APS, such as APS12-2, APS3 (Grandic et al, 2011;Grandic et al, 2013), APS8 (unpublished data) and structurally related compounds, are promising new chemotherapeutic agents that exhibit very low in vivo toxicity in experimental animals. Recently, the effects of some of these synthetic analogs possessing potent AChE-inhibitory properties were studied on neuromuscular transmission in skeletal muscle (reviewed in Grandic and Frangez, 2014) to avoid unwanted peripheral side effects that could appear in patients treated with some AChE inhibitors. APS12-2 acts as a potent non-competitive AChE inhibitor with an inhibitory constant (K i ) of 34 × 10 −3 nM (Houssen et al, 2010).…”

Antistaphylococcal Activities and ADME-Related Properties of Chlorinated Arylcarbamoylnaphthalenylcarbamates

“…This means that the activity only increases to a certain tail length and then decreases. The cut-off effect of the membrane active compounds (which penetrate to the membrane and disrupt its architecture) has been well documented [14,19,20,[36][37][38][39][40][41][42][43][44].…”

“…It can only be speculated whether the different courses of dependences of bactericidal activities against S. aureus ATCC 29213/MRSA SA 3202 (MRSA3) from isolates MRSA1/MRSA2 could be due to their differences in the composition of bacterial membranes [55][56][57][58]. The effect of changing the length of the hydrocarbon tail affecting the extent of antimicrobial activity of the compounds has been discussed (e.g., [36,37,[39][40][41][42][43][44]59,60]). The decrease in biological activity at a higher chain length as a cut-off effect is discussed above.…”