Synthesis of New Dehydrodieugenol Derivatives via Olefin Cross Metathesis and In Vitro Evaluation of Their Trypanocidal Activity

Round 1

Reviewer 1 Report

The manuscript by Lago, Mandelli, Fischmeister, Bruneau descripts cross metathesis reactions of biseugenol with electron-deficient olefins, such as methyl and ethyl acrylates, acrylic acid, acrylonitrile, and methyl methacrylate, catalyzed by the second generation Hoveyda ruthenium catalyst. The conversion of starting materials and the yield of products were reported, which provide data reference for researchers engaged in similar work. More importantly, the activity of these prepared compounds against trypomastigote and amastigote forms of Trypanosoma cruzi and mammalian cytotoxicity have been evaluated. The IC50 values for amastigotes of some products are quite similar to those of biseugenol. Contrasting to the starting material, these prepared compounds exhibited no mammalian toxicity with elevated SI values. These studies fully demonstrate the potential of the synthesized compounds as drugs, and reflect the application value of olefin metathesis reaction in potential drug molecular synthesis. Furthermore, the current manuscript was well prepared. Therefore, I suggest the publication of this manuscript.

The current manuscript was well prepared.

Author Response

We thank this reviewer for the time spent reviewing our manuscript and for the positive review. We have made some corrections in order to improve English language.

Reviewer 2 Report

In the manuscript, the authors describe the synthesis of new dehydrodieugenol derivatives and their biological activity against Trypanosoma cruzi. The most important result presented in the publication is the observed therapeutic activity of the synthesized derivatives. The studies to obtain tri- and tetrasubstituted olefins by cross-metathesis of allyl derivatives with acrylonitrile, acrylates, and methacrylates should now be considered routine. The manuscript contains a very good introduction.

Author Response

We thank this reviewer for the time spent reviewing our manuscript and for the positive review.

Reviewer 3 Report

This manuscript is an interesting study on the synthesis of new dehydrodieugenol derivatives via olefin cross-metathesis with electron deficient olefins. The biological activities of the new prepared compounds against Trypanosoma cruzi are also investigated. The study is well presented and clearly discussed. I think it meets the criteria for acceptance in Catalysts. As minor remarks, some characters like those indicating micromolarities or ppm are lost in the text. In place of them, unclear symbols appear. 

Author Response

We thank this reviewer for the time spent reviewing our manuscript and for the positive review. We have corrected the formatting issues displaying in some places an unknown character instead of "micro" or "ppm". Thank you for spotting this issue.