Design, synthesis, acetylcholinesterase inhibition and larvicidal activity of girgensohnine analogs on Aedes aegypti, vector of dengue fever

Girgensohnine alkaloid was used as a natural model in the design and generation of new alkaloid-like α-aminonitrilea series that was completed by the use of SSA-catalyzed Strecker reaction between commercial and inexpensive substituted benzaldehydes, piperidine (pyrrolidine, morpholine and N-methylpiperazine) and acetone cyanohydrin. Calculated ADMETox parameters of the designed analogs revealed their good pharmacokinetic profiles indicating lipophilic characteristics. In vitro AChE enzyme test showed that obtained a-aminonitriles could be considered as AChEIs with micromolar IC50 values ranging from 42.0 to 478.0 mM (10.3e124.0 mg/mL). Among this series, the best AChE inhibitor was the pyrrolidine a-aminonitrile 3 (IC50 ¼ 42 mM), followed by the piperidine a-aminonitriles 2 and 6 (IC50 ¼ 45 mM and IC50 ¼ 51 mM, respectively), and the compound 7 (IC50 ¼ 51 mM). In vivo insecticidal activity of more active AChEIs against Aedes aegypti larvae was also performed showing a good larvicidal activity at concentrations less than 140 ppm, highlighting products 2 and 7 that could serve as lead compounds to develop new potent and selective insecticides.

Bibliographic Details

Main Authors:	Carreño Otero, Aurora L., Vargas Méndez, Leonor Yamile, Duque L., Jonny Edward, Kouznetsov, Vladimir V.
Format:	Artículo científico biblioteca
Language:	eng
Published:	2014-03
Subjects:	Cromatografía de gases, Aceites vegetales, α-Aminonitriles, Strecker reaction, AChE inhibition, Larvicidal activity, Aedes aegypti larvae, Catalizadores, Bioquímica vegetal, Biotecnología, Química agrícola, Biología molecular,
Online Access:	http://repositorio.colciencias.gov.co/handle/11146/34168
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