Review Reports

Round 1

Reviewer 1 Report

The paper by Lenz et al., describes an interesting interaction between 4,15-iso-atriplicolide esters from the sequiterpene lactone series and the trypanothione-reductase (TR) of Trypanosoma. From an in vitro screening against Trypanosoma brucei, the authors identified a compound exhibiting an IC50 value at 15 nM. It is noteworthy that all the compounds showed a cytotoxicity at less than 10 µM, and can therefore be considered as globally cytotoxic, despite a selectivity index of about 20 for some of them.  Then, the compounds of this series were evaluated on the recombinant TR of Trypanosoma brucei and Trypanosoma cruzi. The mechanism of inhibition was carefully analyzed by using previously described enzymatic methods and the inhibition was found to be irreversible.

Some structure-activity data allow to consider these results as promising and paving the way for new developments in the research for new antitrypanosomal drugs.

I recommend this manuscript for publication in « Molecules ».

Author Response

The authors thank this reviewer for her/his time and the very positive assessment.

Reviewer 2 Report

The manuscript developed by Lenz et al named “Natural Sesquiterpene Lactones of the 4,15-iso-Atriplicolide Type are Inhibitors of Trypanothione Reductase” reported interesting data to be studied and considered in this evaluation. The methodology is well developed and the interpretation of the results as well. Make a review of English for “phrase binding”. I also agree with the conclusion (“The TR28 inhibitory effect by the 4,15-iso-atriplicolide esters thus appears to be specific for this particular type 29 of furanoheliangolide-type STL. Some structure-activity relationships can already be deduced on 30 the basis of the data reported here, which may serve as the starting point for searching further, 31 possibly more potent, TR-inhibitors.)”.
In my opinion, the article (molecules-618118) is accepted for publication in Molecules.

Author Response

The authors thank this reviewer for her/his time and the very positive assessment.