Screening and Application of Chitin Synthase Inhibitors

Round 1

Reviewer 1 Report

 In this research, 35 maleimide compounds were synthesized and their inhibition of CHS activity was analyzed. Some of the synthesized compounds exhibit potent inhibition of CHS activity in vitro and decrease the mycelial growth rate of S. sclerotiorum. The results suggest that maleimide compounds are potential chitin synthase inhibitors. Some concerns need to be addressed before publication.

Main points:

The key conclusion of this manuscript is that some maleimide compounds inhibit chitin synthesis and show antifungal anticity. EC₅₀ values of inhibition of mycelial growth by these compounds were analyzed. First, the correlation of the inhibition of mycelial growth of S. sclerotiorum by these compounds and chitin synthesis needs to be clarified. Second, it would be better to show some representative images for the inhibition of mycelial growth by these compounds.

Minor points:

- A brief explanation of “the least square method” is necessary.

-Line 17: “Thirty five” should be “thirty five” or “35”.

-Line 35: The sentence “can inhibit chitin by inhibiting synthesized to inhibit fungal growth and reproduction” is difficult to understand and needs to be rewrite.

-Line 45: “CHSII” needs to be defined.

-Line 108, 109: “bacterial cell walls” and “bacterial fragments”, should be “fungal”?

-Line 128: “preliminary” should be “previously”.

Author Response

Dear  Reviewer:

      Thank you for your comments concerning our manuscript entitled “Screening and Application of Chitin synthase Inhibitors” (ID: processes-890702). We have studied the comments carefully and have made correction. Please see the attachment about the details.

Author Response File: Author Response.docx

Reviewer 2 Report

In general, this manuscript describes the synthesis and evaluation of a series of compounds as chitin synthase inhibitors and antifungal activity. Despite this manuscript presented interesting findings, there are some aspects that should be ameliorated:

• In the abstract is referred that compound 19 presented and IC₅₀ of 0.12 mM but in table 2 and in the discussion seems to be the compound 20 (not the 19); Please correct as seems that the most promisor compound was the compound 20.
• In figure 1 legend should be added a more complete description of the compounds that were presented.
• In scheme 1 Acotone is acetone?
• In section 2.3.1. should be indicated the 7 concentrations that were used to calculate the IC₅₀ values. 
• Relatively to section 3.1, it is presented a first description of the synthesis conditions but in section 3.1.20 is referred to another description of the synthesis. Probably could be better to put a previous title before each description in order to clarify that the first description is for the first 1-20 compounds and then for the compounds 21-35.
• In section 3.2.1 is referred that the IC₅₀ = 94.5 µg/mL but in table 2 the values were different. Please correct.

Author Response

Dear  Reviewer:

      Thank you for your comments concerning our manuscript entitled “Screening and Application of Chitin synthase Inhibitors” (ID: processes-890702). We have studied the comments carefully and have made correction. Please see the attachment about the details.

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Most of my concerns are addressed in the revised version, but one major issue remains. In the revised version, it is still unclear if the inhibition of mycelial growth of S. sclerotiorum by the compounds is a result of impaired chitin synthesis. The major components of the fungal cell wall include chitin and glucan, thus the synthesis inhibition of either chitin or glucan could impair fungal mycelial growth. Therefore, it is necessary to clarify the cell wall components of S. sclerotiorum and establish the correlation between chitin synthesis and the mycelial growth in this organism.

As suggested, the images of growth inhibition of S. sclerotiorum by some maleimide compounds are included in the revised version in Figure 3. First the concentrations of these images need to be labelled, as the handwriting labels are not decipherable. Moreover, it would be better to include a brief description of the method in the figure legend.

Author Response

Dear Reviewer:

Thank you for your comments concerning our manuscript entitled “Screening and Application of Chitin synthase Inhibitors” (ID: processes-890702). We have studied the comments carefully and have made correction. Please see the attachment about the details.

Author Response File: Author Response.docx