Mefloquine oxazolidine derivatives, derived from mefloquine and arenecarbaldehydes: In vitro activity including against the multidrug-resistant tuberculosis strain T113

Authors: Gonçalves, R.S.B.; Kaiser, C.R.; Lourenço, M.S.C.; Bezerra, F.A.F.M.; De Souza, M.V.N.; Wardell, J.L.; Wardell, S.M.S.V.; Henriques, M.G.M.O.; Costa, T.


Abstract

Ten new mefloquine–oxazolidine derivatives, 4-[(1S,8aR)-3-(aryl)hexahydro[1,3]oxazolo[3,4-a]pyridin-1-yl]-2,8-bis(trifluoromethyl)quinoline (1: aryl = substituted phenyl) and 4-[(1S,8aR)-3-(heteroaryl)hexahydro[1,3]oxazolo[3,4-a]pyridin-1-yl]-2,8-bis(trifluoromethyl)quinoline [2: heteroaryl = 5-nitrothien-2-yl (2a); 5-nitrofuran-2-yl (2b) and 4H-imidazol-2-yl) (2c)], have been synthesized and evaluated against Mycobacterium tuberculosis. Compounds 1f (aryl = 3-ethoxyphenyl), 1g (Ar = 3,4,5-(MeO)3-C6H2) and 2c were slightly more active than mefloquine (MIC = 33 μM) with MICs = 24.5, 22.5 and 27.4, respectively, whereas compounds 1e (aryl = 3,4-(MeO)2-C6H3) and 2a (MICs = 11.9 and 12.1 μM, respectively) were ca. 2.7 times more active than mefloquine, with a better tuberculostatic activity than the first line tuberculostatic agent ethambutol (MIC = 15.9). The compounds were also assayed against the MDR strain T113 and the same MICs were observed. Thus the new derivatives have advantages over such anti-TB drugs as isoniazid, rifampicin, ethambutol and ofloxacin, for which this strain is resistant. The most active compounds were not cytotoxic to Murine Macrophages Cells in a concentration near their MIC values.
Keywords: Multidrug-resistant tuberculosis; Quinoline; Mefloquine
Document Type: Research ArticleDOI: http://dx.doi.org/10.1016/j.bmc.2011.11.006Publication date: 1 de Janeiro de 2012

Compartilhar publicação

Facebook
Twitter
Email
LinkedIn
WhatsApp

Deixe seu comentário

Compartilhar

Sobre a SSCDT

Nosso grupo de pesquisa está situado em Farmanguinhos e atualmente é o maior laboratório farmacêutico oficial vinculado ao Ministério da Saúde. Farmanguinhos produz mais de um bilhão de medicamentos por ano para os programas estratégicos do Governo Federal, além de atender demandas emergenciais no Brasil e no exterior.

posts Recentes