Silva, DárioLopes, Márcio V. C.Petrovski, ŽeljkoSantos, Miguel M.Santos, Jussevania P.Yamada-Ogatta, Sueli F.Bispo, Marcelle L. F.de Souza, Marcus V. N.Duarte, Ana Rita C.Lourenço, Maria C. S.Gonçalves, Raoni Schroeder B.Branco, Luís C.2023-03-162023-03-162022-08-131420-3049PURE: 56135786PURE UUID: 5415aae6-5387-468c-b939-a215802ac8f1Scopus: 85136609871PubMed: 36014405PubMedCentral: PMC9412322WOS: 000845315900001ORCID: /0000-0003-0800-0112/work/131002329ORCID: /0000-0002-8104-7008/work/131002362ORCID: /0000-0001-8973-1595/work/131002471http://hdl.handle.net/10362/150735Funding Information: This work was supported by FCT-MCTES (PEst-C/LA0006/2013, RECI/BBBBQB/0230/2012). The NMR spectrometers are part of the National NMR Network (PTNMR) and are partially supported by Infrastructure Project N° 022161 (co-financed by FEDER through COMPETE 2020, POCI, PORL, and FCT through PIDDAC). Publisher Copyright: © 2022 by the authors.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]).15970884engAPI-OSILsionic liquidsmefloquinepolymorphismtuberculosisAnalytical ChemistryChemistry (miscellaneous)Molecular MedicinePharmaceutical ScienceDrug DiscoveryPhysical and Theoretical ChemistryOrganic ChemistrySDG 3 - Good Health and Well-beingjournal article10.3390/molecules27165167https://www.scopus.com/pages/publications/85136609871