Annual Activities Report 2011 - INCT-Inofar - UFRJ

Annual Report 2011 | INCT-INOFAR
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Highlights
A sensitive, specific and accurate method is first described for the quantification of the cardioactive
prototype L-294 in dog plasma by LC–MS/MS in positive electrospray ionization mode using MRM and
fully validated according to commonly accepted criteria. The method exhibited excellent performance in
terms of high selectivity, low LLOQ (1.25 ng/mL), wide linear range (1.25–800 ng/mL), small organic
solvent consumption (720 μL) and small plasma volume (200 μL). Moreover, the method has been
successfully used for a pre-clinical pharmacokinetic study in dogs after oral administration of L-294.
The pharmacokinetic parameters obtained from this study can give some useful information for further
research of L-294.
Anticholinesterasic, nematostatic and
anthelmintic activities of pyridinic and
pyrazinic compounds
Valli M.; DanuelloA.; Pivatto M.; Saldaña J.C.; Heinzen H.; Domínguez L.; Campos V.P.; Marqui S.R.;
Young M.C.M.; Viegas Jr. C.; Silva D.H.S.; Bolzani V.S. Current Medicinal Chemistry. 18 (2011) 3423-
3430. DOI:10.2174/092986711796504718
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 (Fig. 1).
Fig. (1). Typical hybrid product (9) formed by molecular hybridization of tacrine (1) and
(–)-3-O-acetylspectaline (2).
The synthesized compounds (Scheme 1) presented moderate anticholinesterasic activities when compared
with the positive control physostigmine. One compound (ethyl 2-[(6-chloropyrazin-2-yl)sulfanyl] acetate,
11) exhibited an in vitro ability to immobilize the root-knot nematode Meloidogyne incognita that was