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.
Source: Bioorganic & Medicinal Chemistry (Print), v. 20, p. 243-248, 2012.
Publisher: Elsevier
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 Article DOI: http://dx.doi.org/10.1016/j.bmc.2011.11.006 Publication date: 1 de Janeiro de 2012
