Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

3-Alkylpyridinium polymers (poly-APS), composed of 29 or 99 N-butyl-3-butyl pyridinium units, were isolated from the marine sponge Reniera sarai. They act as potent cholinesterase inhibitors. The inhibition kinetics pattern reveals several successive phases ending in irreversible inhibition of the enzyme. To provide more information on mechanism of inhibition, interaction of poly-APS and N-butyl-3-butyl pyridinium iodide (NBPI) with soluble dimeric and monomeric insect acetylcholinesterase (AChE) was studied by using enzyme intrinsic fluorescence and light scattering, conformational probes ANS and trypsin, and SDS-PAGE. Poly-APS quenched tryptophan fluorescence emission of AChE more extensively than NBPI. Both inhibitors exhibited a pseudo-Lehrer type of quenching. Interaction of poly-APS with dimeric AChE did not induce significant changes of the enzyme conformation as assayed by using the hydrophobic probe ANS and trypsin digestion. In contrast to NBPI, titration of both monomeric and dimeric AChE with poly-APS resulted in the appearance of large complexes detected by measuring light scattering. An excess of poly-APS produced AChE precipitation as proved on SDS-PAGE. None of the effects were observed with trypsin as a control. It was concluded that AChE aggregation and precipitation rather than the enzyme conformational changes accounted for the observed irreversible component of poly-APS inhibition.
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PMID:Interaction of 3-alkylpyridinium polymers from the sea sponge Reniera sarai with insect acetylcholinesterase. 1039 43

Water soluble polymeric 3-alkylpyridinium salts (poly APS; MW 18900 and 5520 Da) were isolated from the marine sponge Raniera sarai. In vitro it strongly inhibited acetyl cholinesterase (AChE) from different species (electric eel, horse serum, human erythrocytes). In our experiments the importance of anti AChE activity in the toxin lethality was evaluated. In vivo experiments were performed on male Wistar rats and ECG, blood pressure and breathing pattern were monitored. After i.v. application of lethal doses of the toxin ECG showed signs of hypo perfusion. Arterial blood pressure fell to mid-circulatory pressure, and breathing stopped after a few breaths At sublethal doses the toxin caused an increase of residual volume, prolongation of expiration, and bradycardia. Patho-anatomical examination revealed that the plugs in lung circulation may cause the death of experimental animals due to cardiorespiratory failure.
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PMID:In vivo effects of head-to-tail 3-alkylpiridinium polymers isolated from the marine sponge Raniera sarai. 1100 59

Previous studies have shown that the cholinergic system plays a pivotal rule in small cell lung cancer (SCLC) cell growth through an autocrine loop that activates the nicotinic cholinergic receptor, which together with the activation of this receptor by nicotine links SCLC evolution with tobacco use. Non-small cell lung cancer (NSCLC) is the most common form of lung cancer and is also linked to tobacco use. Here we describe the presence of molecules of the cholinergic system in NSCLC samples and cell lines and investigate the implications of the cholinergic system in cell growth regulation. Cholino-acetyltransferase (ChAT), vesicular acetylcholine transporter (VAChT) and acetylcholinesterase (AChE) were observed in NSCLC tumor biopsies and in NSCLC cell lines. Polymeric alkylpyridinium salts (poly-APS) are AChE inhibitors isolated from the crude extract of the marine sponge, Reniera sarai. These metabolites were characterized as a mixture of two polymers of 3-octylpyridinium, including 29 and 99 monomeric units. Exposure of normal lung fibroblast and NSCLC cell lines to poly-APS revealed a selective cytotoxicity for cancer cells as compared to the normal fibroblast cell lines. FACS analysis indicated poly-APS induced apoptosis in NSCLC cells but not in normal lymphocytes. Non-toxic doses of poly-APS also potently reduced NSCLC cell-cell adhesion in suspension cultures. The limited toxicity of poly-APS on normal cells was confirmed by injection in the caudal vein of mice. No overt effects on health parameters, such as weight gain and physical behavior, were observed, and histological analysis of major organs did not reveal differences between the treated animals as compared to controls. These data demonstrate that NSCLC cells express cholinergic molecules that may be involved in cell growth regulation and that the cholinesterase inhibitor, poly-APS, shows selective toxicity toward NSCLC cells while having no apparent toxicity towards normal cells and tissue in vitro and in vivo.
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PMID:Marine sponge-derived polymeric alkylpyridinium salts as a novel tumor chemotherapeutic targeting the cholinergic system in lung tumors. 1708 75

Polymeric 3-alkylpyridinium salts (poly-APS) present in the marine sponge Reniera sarai show a broad spectrum of biological activities. They are lytic to erythrocytes and various other mammalian cells, enabling the transfection of the latter with alien DNA. Furthermore, they show inhibitory effects to marine bacteria and can inhibit fouling of micro- and macroorganisms to submerged surfaces. Finally, poly-APS act as potent cholinesterase inhibitors. The kinetics of acetylcholinesterase inhibition by poly-APS in vitro is complex and comprises several successive phases ending in irreversible inhibition of the enzyme. The latter is accounted for by aggregation and precipitation of the enzyme-inhibitor complexes. Poly-APS are lethal to rats in concentrations above 2.7 mg/kg. Monitoring of the basic vital functions and histopathological analysis showed that the effects directly ascribable to acetylcholinesterase inhibition are only observed after application of lower concentrations of poly-APS. At higher concentrations, such effects were masked by other, more pronounced and faster developing lethal effects of the toxin, such as haemolysis and platelet aggregation.
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PMID:Mechanisms of toxicity of 3-alkylpyridinium polymers from marine sponge Reniera sarai. 1846 30

Water soluble polymeric 3-alkylpyridinium salts (poly APS; MW 18900 and 5520 Da) were isolated from the marine sponge Raniera sarai. In vitro it strongly inhibited acetyl cholinesterase (AChE) from different species (electric eel, horse serum, human erythrocytes). In our experiments the importance of anti AChE activity in the toxin lethality was evaluated. In vivo experiments were performed on male Wistar rats and ECG, blood pressure and breathing pattern were monitored. After i.v. application of lethal doses of the toxin ECG showed signs of hypo perfusion. Arterial blood pressure fell to mid-circulatory pressure, and breathing stopped after a few breaths At sublethal doses the toxin caused an increase of residual volume, prolongation of expiration, and bradycardia. Patho-anatomical examination revealed that the plugs in lung circulation may cause the death of experimental animals due to cardiorespiratory failure.
 ...
PMID:In vivo effects of head-to-tail 3-alkylpiridinium polymers isolated from the marine sponge Raniera sarai. 2800 28