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https://www.arca.fiocruz.br/handle/icict/61470
NOVEL ORGANIC SALTS BASED ON MEFLOQUINE: SYNTHESIS, SOLUBILITY, PERMEABILITY, AND IN VITRO ACTIVITY AGAINST MYCOBACTERIUM TUBERCULOSIS
Author
Affilliation
NOVA School of Science and Technology. Department of Chemistry. LAQV-REQUIMTE. Caparica, Portugal.
Universidade Federal do Rio de Janeiro. Instituto de Química. Rio de Janeiro, RJ, Brasil.
NOVA School of Science and Technology. Department of Chemistry. LAQV-REQUIMTE. Caparica, Portugal.
NOVA School of Science and Technology. Department of Chemistry. LAQV-REQUIMTE. Caparica, Portugal.
Universidade Estadual de Londrina. Departamento de Microbiologia. Londrina, PR, Brasil.
Universidade Estadual de Londrina. Departamento de Microbiologia. Londrina, PR, Brasil.
Universidade Estadual de Londrina. Departamento de Microbiologia. Londrina, PR, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos (Farmanguinhos). Rio de Janeiro, RJ, Brasil.
NOVA School of Science and Technology. Department of Chemistry. LAQV-REQUIMTE. Caparica, Portugal.
Fundação Oswaldo Cruz. Instituto de Pesquisas Clínicas Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Química. Rio de Janeiro, RJ, Brasil.
NOVA School of Science and Technology. Department of Chemistry. LAQV-REQUIMTE. Caparica, Portugal.
Universidade Federal do Rio de Janeiro. Instituto de Química. Rio de Janeiro, RJ, Brasil.
NOVA School of Science and Technology. Department of Chemistry. LAQV-REQUIMTE. Caparica, Portugal.
NOVA School of Science and Technology. Department of Chemistry. LAQV-REQUIMTE. Caparica, Portugal.
Universidade Estadual de Londrina. Departamento de Microbiologia. Londrina, PR, Brasil.
Universidade Estadual de Londrina. Departamento de Microbiologia. Londrina, PR, Brasil.
Universidade Estadual de Londrina. Departamento de Microbiologia. Londrina, PR, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos (Farmanguinhos). Rio de Janeiro, RJ, Brasil.
NOVA School of Science and Technology. Department of Chemistry. LAQV-REQUIMTE. Caparica, Portugal.
Fundação Oswaldo Cruz. Instituto de Pesquisas Clínicas Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Química. Rio de Janeiro, RJ, Brasil.
NOVA School of Science and Technology. Department of Chemistry. LAQV-REQUIMTE. Caparica, Portugal.
Abstract
The development of novel pharmaceutical tools to efficiently tackle tuberculosis is the order of the day due to the rapid development of resistant strains of Mycobacterium tuberculosis. Herein, we report novel potential formulations of a repurposed drug, the antimalarial mefloquine (MFL), which was combined with organic anions as chemical adjuvants. Eight mefloquine organic salts were obtained by ion metathesis reaction between mefloquine hydrochloride ([MFLH][Cl]) and several
organic acid sodium salts in high yields. One of the salts, mefloquine mesylate ([MFLH][MsO]), presented increased water solubility in comparison with [MFLH][Cl]. Moreover, all salts with the exception of mefloquine docusate ([MFLH][AOT]) showed improved permeability and diffusion through synthetic membranes. Finally, in vitro activity studies against Mycobacterium tuberculosis revealed that these ionic formulations exhibited up to 1.5-times lower MIC values when compared with [MFLH][Cl], particularly mefloquine camphorsulfonates ([MFLH][(1R)-CSA], [MFLH][(1S)-CSA]) and mefloquine HEPES ([MFLH][HEPES]).
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