N-phenyl-6-chloro-4-hydroxy-2-quinolone-3-carboxamides: Molecular Docking, Synthesis, and Biological Investigation as Anticancer Agents

Round 1

Reviewer 1 Report

The article presented is very interesting. It presents a series of new compounds as potential agents in the fight against cancer. The compounds are well characterized and very well described. The methodology used is valid and is very well discussed. However, there appears to be a lack of information in the introduction. In this section it makes reference to cancer and the whole problem, they refer to the target that they are going to test but do not make a relation with the colorectal cancer, since later they will test the compounds in two colon lines (Caco2 and HCT116). This point should be explained by the authors. Overall, the article is interesting and should be published after the suggested changes.

Author Response

Dear Dr. Isabelle Mus-Veteau,

Thank you for your letter and constructive comments concerning our manuscript entitled " N-Phenyl-6-Chloro-4-Hydroxy-2-Quinolone-3-Carboxamides: Molecular Docking, Synthesis, and Biological Investigation as Anticancer Agents". We have addressed your comments carefully and made major corrections which we hope meet with your approval. Please consider our point-by-point responses to the reviewers in the following texts.

Author Response File: Author Response.pdf

Reviewer 2 Report

The manuscript by Sabbah et al reports on the synthesis of eighteen derivatives of N-phenyl-6-chloro-4-hydroxy-2-quinolone-3-carboxamide evaluated for their antiproliferative activity on Caco-2 and HTC-116 cell lines. In my opinion the paper is suitable for publication on Molecules after major revisions. 

First of all, I think that the rationale that led to the synthesis of the 6-chloro derivatives is missing. The authors state that they decided to synthesize these derivatives but they do not explain which are the reasons of this choice. In fact, no mention on the effect of this insertion has been done in the discussion of the biological results, neither in the molecular modeling section. Moreover, the biological results has to be compared with those of compound 1, that represents the lead of this series of molecules.

The discussion section, and in particular, the SAR section has to be improved. Molecular docking studies, for example, will help to understand the difference in biological activity observed for the regioisomers 16 and 17, or to explain the great difference between the activities of the -COOH substituted derivatives 13-15 and 22-24 with respect to compound 18. 

Finally, some comments has to be done in order to justify the difference in the inhibitory activity towards Caco-2 and HCT-116 cells. 

Author Response

Dear Dr. Isabelle Mus-Veteau,

Thank you for your letter and constructive comments concerning our manuscript entitled " N-Phenyl-6-Chloro-4-Hydroxy-2-Quinolone-3-Carboxamides: Molecular Docking, Synthesis, and Biological Investigation as Anticancer Agents". We have addressed your comments carefully and made major corrections which we hope meet with your approval. Please consider our point-by-point responses to the reviewers in the following texts.

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

The authors addressed my concerns. 

The manuscript can be published in the present form.