title: Anticholinesterasic, nematostatic and anthelmintic activities of pyridinic and pyrazinic compounds.
abstract: In the search for acetylcholinesterase inhibitors as a potential target for the discovery of anthelmintic drugs, a series of 27 pyridinic and pyrazinic compounds have been designed on the basis of molecular hybridization of two known AChE inhibitors, namely, tacrine and (-)-3-O-acetylspectaline, and on the concept of isosterism. The synthesized compounds generally presented moderate anticholinesterasic activities when compared with the positive control physostigmine, but one compound (ethyl 2-[(6-chloropyrazin-2-yl)sulfanyl] acetate) exhibited an in vitro ability to immobilize the root-knot nematode Meloidogyne incognita that was highly comparable to that of the positive control Temik. Moreover, in anthelmintic assays against the gastrointestinal parasitic nematode Nippostrongylus brasiliensis (L4), some of the compounds, such as (6-chloropyrazin-2-yl)sulfanyl ethanol (32, EC₅₀ = 33 nM), presented activities that were considerably stronger than that of the positive control albendazole (EC₅₀ = 340 nM). In the light of the positive results obtained in the anthelmintic evaluations, the acute oral toxicity of the representative compound diethyl 2,2'-[(3-nitropyridine-2,6-diyl) bissulfanediyl] diacetate was determined in rats, and the drug was shown to be non-toxic at a dose of 2000 mg/kg. These results, allied with the relatively simple structures of the active compounds and their facile synthesis, highlight their potential use as anthelmintic or nematicidic agents.
authors: Departamento de Química, Núcleo de Bioensaios, Biossíntese e Ecofisiologia de Produtos Naturais (NuBBE), Instituto de Química, UNESP-Universidade Estadual Paulista, C.P. 355, 14801-970, Araraquara, SP, Brazil.
authors: M
authors: M
authors: Valli
authors: A
authors: A
authors: Danuello
authors: M
authors: M
authors: Pivatto
authors: J C
authors: JC
authors: Saldaña
authors: H
authors: H
authors: Heinzen
authors: L
authors: L
authors: Domínguez
authors: V P
authors: VP
authors: Campos
authors: S R
authors: SR
authors: Marqui
authors: M C M
authors: MC
authors: Young
authors: C
authors: C
authors: Viegas
authors: D H S
authors: DH
authors: Silva
authors: V S
authors: VS
authors: Bolzani
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000737:chemistry* / Q000494:pharmacology; D000969:Antinematodal Agents / Q000737:chemistry* / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D021261:Parasitic Sensitivity Tests; D011719:Pyrazines / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000871:Anthelmintics; D000969:Antinematodal Agents; D002800:Cholinesterase Inhibitors; D011719:Pyrazines; D011725:Pyridines