4-Alkoxybenzamidines as new potent phospholipase A2 inhibitors

Biochemical Pharmacology
M AitdafounJ J Godfroid

Abstract

A series of 4-alkoxybenzamidines was synthesized, varying the number of carbons of the alkyl chain, and their potency as phospholipase A2 (PLA2) inhibitors was evaluated. The relationship between their capacity to inhibit PLA2 activity and their lipophilicity was examined. The optimum of the inhibitory effect against two extracellular PLA2S from rabbit platelets and bovine pancreas was observed with compounds bearing an alkyl chain of 12 and 14 carbons. These 4-dodecyl and tetradecyloxbenzamidines inhibited bovine pancreatic and rabbit platelet lysate PLA2S with IC50 values of 3 microM and 5-5.8 microM, respectively. The mechanism of inhibition was of the competitive type. In addition, 4-tetradecyloxbenzamidine was shown to exert an antiinflammatory effect in vivo on the carrageenan-induced rat paw oedema. These results show that 4-tetradecyloxybenzamidine will serve as an interesting tool to investigate the physiological role of mammalian-secreted PLA2, both in vitro and in vivo.

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Citations

Feb 7, 1997·Biochemical Pharmacology·S Legrand-PoelsJ Piette
Oct 19, 2010·Natural Product Research·Chhaya Gadgoli, Sandeep Shelke
Sep 26, 2012·Scientia pharmaceutica·Santosh Singh BhadoriyaSunil K Jain
Jul 27, 2010·Journal of Ethnopharmacology·Menuka ArawwawalaShiroma Handunnetti
Dec 7, 2007·Journal of Ethnopharmacology·Solomon Umukoro, Babatunde Rasaq Ashorobi
Jun 1, 2012·Evidence-based Complementary and Alternative Medicine : ECAM·Chattopadhyay DebprasadChakraborti Sekhar
Nov 23, 2018·Biomedicines·K D P P GunathilakeH P Vasantha Rupasinghe
Jan 8, 2000·The Journal of Biological Chemistry·P G HainsK W Broady

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