Novel Organic Salts Based on Mefloquine: Synthesis, Solubility, Permeability, and In Vitro Activity against <i>Mycobacterium tuberculosis</i>
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 <i>Mycobacterium tuberculosis</i>. Herein, we report novel potential formulations of a repurposed drug, the antimalarial mefloquin...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-08-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/27/16/5167 |
| _version_ | 1797408731883896832 |
|---|---|
| author | Dário Silva Márcio V. C. Lopes Željko Petrovski Miguel M. Santos Jussevania P. Santos Sueli F. Yamada-Ogatta Marcelle L. F. Bispo Marcus V. N. de Souza Ana Rita C. Duarte Maria C. S. Lourenço Raoni Schroeder B. Gonçalves Luis C. Branco |
| author_facet | Dário Silva Márcio V. C. Lopes Željko Petrovski Miguel M. Santos Jussevania P. Santos Sueli F. Yamada-Ogatta Marcelle L. F. Bispo Marcus V. N. de Souza Ana Rita C. Duarte Maria C. S. Lourenço Raoni Schroeder B. Gonçalves Luis C. Branco |
| author_sort | Dário Silva |
| collection | DOAJ |
| description | 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 <i>Mycobacterium tuberculosis</i>. 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 <i>Mycobacterium tuberculosis</i> revealed that these ionic formulations exhibited up to 1.5-times lower MIC values when compared with [MFLH][Cl], particularly mefloquine camphorsulfonates ([MFLH][(1<i>R</i>)-CSA], [MFLH][(1<i>S</i>)-CSA]) and mefloquine HEPES ([MFLH][HEPES]). |
| first_indexed | 2024-03-09T04:02:47Z |
| format | Article |
| id | doaj.art-a6a4378ca57e49f6ae1230e45fe18e10 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T04:02:47Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-a6a4378ca57e49f6ae1230e45fe18e102023-12-03T14:11:18ZengMDPI AGMolecules1420-30492022-08-012716516710.3390/molecules27165167Novel Organic Salts Based on Mefloquine: Synthesis, Solubility, Permeability, and In Vitro Activity against <i>Mycobacterium tuberculosis</i>Dário Silva0Márcio V. C. Lopes1Željko Petrovski2Miguel M. Santos3Jussevania P. Santos4Sueli F. Yamada-Ogatta5Marcelle L. F. Bispo6Marcus V. N. de Souza7Ana Rita C. Duarte8Maria C. S. Lourenço9Raoni Schroeder B. Gonçalves10Luis C. Branco11LAQV-REQUIMTE, Department of Chemistry, NOVA School of Science and Technology, 2829-516 Caparica, PortugalInstituto de Química, Universidade Federal do Rio de Janeiro, Av. Athos da Silveira Ramos 149, Cidade Universitaria, Rio de Janeiro 21941-909, BrazilLAQV-REQUIMTE, Department of Chemistry, NOVA School of Science and Technology, 2829-516 Caparica, PortugalLAQV-REQUIMTE, Department of Chemistry, NOVA School of Science and Technology, 2829-516 Caparica, PortugalDepartamento de Microbiologia, Universidade Estadual de Londrina, Rodovia Celso Garcia Cid (PR 445), Km 380, Campus Universitário, Londrina 86057-970, BrazilDepartamento de Microbiologia, Universidade Estadual de Londrina, Rodovia Celso Garcia Cid (PR 445), Km 380, Campus Universitário, Londrina 86057-970, BrazilDepartamento de Microbiologia, Universidade Estadual de Londrina, Rodovia Celso Garcia Cid (PR 445), Km 380, Campus Universitário, Londrina 86057-970, BrazilFioCruz-Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos-Far-Manguinhos, Rua Sizenando Nabuco, 100, Manguinhos, Rio de Janeiro 21041-250, BrazilLAQV-REQUIMTE, Department of Chemistry, NOVA School of Science and Technology, 2829-516 Caparica, PortugalInstituto de Pesquisas Clínica Evandro Chagas—IPEC, Av. Brasil, 4365, Manguinhos, Rio de Janeiro 21040-900, BrazilInstituto de Química, Universidade Federal do Rio de Janeiro, Av. Athos da Silveira Ramos 149, Cidade Universitaria, Rio de Janeiro 21941-909, BrazilLAQV-REQUIMTE, Department of Chemistry, NOVA School of Science and Technology, 2829-516 Caparica, PortugalThe development of novel pharmaceutical tools to efficiently tackle tuberculosis is the order of the day due to the rapid development of resistant strains of <i>Mycobacterium tuberculosis</i>. 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 <i>Mycobacterium tuberculosis</i> revealed that these ionic formulations exhibited up to 1.5-times lower MIC values when compared with [MFLH][Cl], particularly mefloquine camphorsulfonates ([MFLH][(1<i>R</i>)-CSA], [MFLH][(1<i>S</i>)-CSA]) and mefloquine HEPES ([MFLH][HEPES]).https://www.mdpi.com/1420-3049/27/16/5167API-OSILsionic liquidsmefloquinepolymorphismtuberculosis |
| spellingShingle | Dário Silva Márcio V. C. Lopes Željko Petrovski Miguel M. Santos Jussevania P. Santos Sueli F. Yamada-Ogatta Marcelle L. F. Bispo Marcus V. N. de Souza Ana Rita C. Duarte Maria C. S. Lourenço Raoni Schroeder B. Gonçalves Luis C. Branco Novel Organic Salts Based on Mefloquine: Synthesis, Solubility, Permeability, and In Vitro Activity against <i>Mycobacterium tuberculosis</i> Molecules API-OSILs ionic liquids mefloquine polymorphism tuberculosis |
| title | Novel Organic Salts Based on Mefloquine: Synthesis, Solubility, Permeability, and In Vitro Activity against <i>Mycobacterium tuberculosis</i> |
| title_full | Novel Organic Salts Based on Mefloquine: Synthesis, Solubility, Permeability, and In Vitro Activity against <i>Mycobacterium tuberculosis</i> |
| title_fullStr | Novel Organic Salts Based on Mefloquine: Synthesis, Solubility, Permeability, and In Vitro Activity against <i>Mycobacterium tuberculosis</i> |
| title_full_unstemmed | Novel Organic Salts Based on Mefloquine: Synthesis, Solubility, Permeability, and In Vitro Activity against <i>Mycobacterium tuberculosis</i> |
| title_short | Novel Organic Salts Based on Mefloquine: Synthesis, Solubility, Permeability, and In Vitro Activity against <i>Mycobacterium tuberculosis</i> |
| title_sort | novel organic salts based on mefloquine synthesis solubility permeability and in vitro activity against i mycobacterium tuberculosis i |
| topic | API-OSILs ionic liquids mefloquine polymorphism tuberculosis |
| url | https://www.mdpi.com/1420-3049/27/16/5167 |
| work_keys_str_mv | AT dariosilva novelorganicsaltsbasedonmefloquinesynthesissolubilitypermeabilityandinvitroactivityagainstimycobacteriumtuberculosisi AT marciovclopes novelorganicsaltsbasedonmefloquinesynthesissolubilitypermeabilityandinvitroactivityagainstimycobacteriumtuberculosisi AT zeljkopetrovski novelorganicsaltsbasedonmefloquinesynthesissolubilitypermeabilityandinvitroactivityagainstimycobacteriumtuberculosisi AT miguelmsantos novelorganicsaltsbasedonmefloquinesynthesissolubilitypermeabilityandinvitroactivityagainstimycobacteriumtuberculosisi AT jussevaniapsantos novelorganicsaltsbasedonmefloquinesynthesissolubilitypermeabilityandinvitroactivityagainstimycobacteriumtuberculosisi AT suelifyamadaogatta novelorganicsaltsbasedonmefloquinesynthesissolubilitypermeabilityandinvitroactivityagainstimycobacteriumtuberculosisi AT marcellelfbispo novelorganicsaltsbasedonmefloquinesynthesissolubilitypermeabilityandinvitroactivityagainstimycobacteriumtuberculosisi AT marcusvndesouza novelorganicsaltsbasedonmefloquinesynthesissolubilitypermeabilityandinvitroactivityagainstimycobacteriumtuberculosisi AT anaritacduarte novelorganicsaltsbasedonmefloquinesynthesissolubilitypermeabilityandinvitroactivityagainstimycobacteriumtuberculosisi AT mariacslourenco novelorganicsaltsbasedonmefloquinesynthesissolubilitypermeabilityandinvitroactivityagainstimycobacteriumtuberculosisi AT raonischroederbgoncalves novelorganicsaltsbasedonmefloquinesynthesissolubilitypermeabilityandinvitroactivityagainstimycobacteriumtuberculosisi AT luiscbranco novelorganicsaltsbasedonmefloquinesynthesissolubilitypermeabilityandinvitroactivityagainstimycobacteriumtuberculosisi |