Novel Organic Salts Based on Mefloquine: Synthesis, Solubility, Permeability, and In Vitro Activity against Mycobacterium tuberculosis
, Márcio V. C. Lopes 2, Željko Petrovski 1, Miguel M. Santos 1, Jussevania P. Santos 3, Sueli F. Yamada-Ogatta 3, Marcelle L. F. Bispo 3, Marcus V. N. de Souza 4, Ana Rita C. Duarte 1, Maria C. S. Lourenço 5, Raoni Schroeder B. Gonçalves 2,* and Luis C. Branco 1,*Round 1
Reviewer 1 Report
The paper is very interesting and well written.
The topic is appropriate for the journal.
Author Response
Thank you for your comments.
Reviewer 2 Report
This work is devoted to the preparation and study of organic salts based on mefloquine. The authors studied in detail the synthesis process, solubility and biological activity of the obtained substances. Abstract is fully described by the authors. The introduction makes it easy to understand the problematics of the issue and the need for research by the authors. Abundant literary references - plus in the introduction and in the description of the results, which gives greater validity to everything that has been done in this work. There are some small notes that can be tired:
1. NMR and FTIR Spectra can be described in more detail in the text.
2. Part of the information from "Supporting information" can be transferred to the main text.
3. Please cite: 10.1016/j.jksus.2021.101807
4. Recommendation for further research: It would be interesting to study these substances by quantum chemical methods in order to obtain more information about the physicochemical characteristics.
5. In the biological activity part, more references to the literature can be added. What known substances can be compared with those obtained by the authors?
6. Conclusions need to be substantially expanded. One sentence in the conclusions is too little.
Author Response
Thank you for your comments about the manuscript.
The reviewer considers that “This work is devoted to the preparation and study of organic salts based on mefloquine. The authors studied in detail the synthesis process, solubility and biological activity of the obtained substances. Abstract is fully described by the authors. The introduction makes it easy to understand the problematics of the issue and the need for research by the authors. Abundant literary references - plus in the introduction and in the description of the results, which gives greater validity to everything that has been done in this work.”
About the small notes mentioned by reviewer:
R1. NMR and FTIR Spectra can be described in more detail in the text.
Authors: An additional paragraph was added to the text.
R2. Part of the information from "Supporting information" can be transferred to the main text.
Authors: The authors decided to not transfer the SI to main text because the manuscript is too long and the information data in the SI is well-presented and complementary to the information from the manuscript.
R3. Please cite: 10.1016/j.jksus.2021.101807
Authors: After careful analysis of the mentioned reference, We decided that this article is not aligned with our studies and difficult to cite in this context.
R4. Recommendation for further research: It would be interesting to study these substances by quantum chemical methods in order to obtain more information about the physicochemical characteristics.
Authors: Thank you for your recommendation. We are interested to perform some quantum chemical methods to predict physicochemical properties and we hope to show new data as soon as possible.
R5. In the biological activity part, more references to the literature can be added. What known substances can be compared with those obtained by the authors?
Authors: According to our knowledge, the available literature to compare the biological activity data were included in the manuscript.
R6. Conclusions need to be substantially expanded. One sentence in the conclusions is too little.
Authors: The following sentences were included in the conclusions part:
“In this work different MFL salts based on direct protonation of the original drug by the use of organic sulfonic acids have been developed. The spectroscopic techniques such as NMR, FTIR-ATR and elemental analysis proof the desired chemical structures. It is important to note that mefloquine mesylate ([MFLH][MsO]), presented increased water solubility in comparison with [MFLH][Cl]. Moreover, almost all salts showed improved permeability and diffusion through synthetic membranes except in the case of mefloquine docusate.”
Best regards
