TY - JOUR
T1 - Novel Organic Salts Based on Mefloquine
T2 - Synthesis, Solubility, Permeability, and In Vitro Activity against Mycobacterium tuberculosis
AU - Silva, Dário
AU - Lopes, Márcio V. C.
AU - Petrovski, Željko
AU - Santos, Miguel M.
AU - Santos, Jussevania P.
AU - Yamada-Ogatta, Sueli F.
AU - Bispo, Marcelle L. F.
AU - de Souza, Marcus V. N.
AU - Duarte, Ana Rita C.
AU - Lourenço, Maria C. S.
AU - Gonçalves, Raoni Schroeder B.
AU - Branco, Luís C.
N1 - info:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FQUI-QOR%2F32406%2F2017/PT#
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F50006%2F2020/PT#
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F50006%2F2020/PT#
Funding 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.
PY - 2022/8/13
Y1 - 2022/8/13
N2 - 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]).
AB - 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]).
KW - API-OSILs
KW - ionic liquids
KW - mefloquine
KW - polymorphism
KW - tuberculosis
UR - http://www.scopus.com/inward/record.url?scp=85136609871&partnerID=8YFLogxK
U2 - 10.3390/molecules27165167
DO - 10.3390/molecules27165167
M3 - Article
C2 - 36014405
AN - SCOPUS:85136609871
SN - 1420-3049
VL - 27
JO - Molecules
JF - Molecules
IS - 16
M1 - 5167
ER -
