Annual Activities Report 2011 - INCT-Inofar - UFRJ

Annual Report 2011 | INCT-INOFAR
Highlights
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, EC 50
= 33 nM), presented activities that were considerably
stronger than that of the positive control albendazole (EC 50
= 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 (7) 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.
Scheme (1). Synthesis of compounds 7 - 33. Reagents and conditions: a) ethyl-2-mercaptoacetate,
NaH, anhydrous THF, N 2
atmosphere, room temperature or ice bath, depending on the reaction, for 5
min to 12 h, depending on the starting material; b) NaOH, EtOH/H 2
O (2:1), room temperature for
1 h; c) alcohol (MeOH, n-PrOH or n-BuOH), H 2
SO 4
, reflux for 12 h; d) LiAlH 4
, anhydrous THF, N 2
atmosphere, ice bath for 12 h; e) Feo, NH 4
Cl, EtOH/H 2
O (2:1), reflux for 90 min.
Table 1. In vitro AChE inhibitory, nematostatic and anthelmintic activities of the most active compounds.
Compound
AChE inhibition (LOD, M. Incognita N. brasiliensis death
nmol)
immobilization (%) (EC 50
, nM)
7 8.6 12 56.0
10 - 19 34.0
11 13.0 98 -
17 - - 230.0
18 - - -
21 - - 60.0
26 12.0 - 69.0
32 130.0 - 33.0
a
physostigmine | b Temik | c albendazole
55
Patent
LC Dias, AS Vieira, EJ Barreiro, Process for obtaining calcium atorvastatin using novel intermediates, PI
018110015039 (INPI, in 04/25/2011), PCT in december, 2011.