Potent Tyrosinase Inhibitory Activity of Curcuminoid Analogues and Inhibition Kinetics Studies

Round 1

Reviewer 1 Report

The work is of an experimental nature and this in itself is very valuable. It presents interesting, in my opinion, data from biochemical studies.
However, the interpretation of the relationship between the structure and anti-tyrosinase activity of curcumin derivatives is presented somewhat unclear.
In my opinion, the material would be perceived more clearly if the authors would graphically highlight the structural fragments discussed in the text in a separate figure and show schematically their contribution to the property under study. I mean, the authors, in my opinion, can show by arrows pointing down and up, structural fragments that decrease and increase the antityrosinase activity, respectively.
In my opinion, the work is complete. But it needs a clearer visualization of the SAR data.

Author Response

We thank the reviewer for these valuable suggestions. We agree with the reviewer’s opinion, and we have now included in the text a graphic highlighting our SAR studies of the curcuminoid analogues (Figure 1). The numbers of Figures have now been changed from Figures 1-3 to Figures 2-4, respectively.

Author Response File: Author Response.pdf

Reviewer 2 Report

An interesting original study exploring the role of biochemical analogs of Curcuma longa as potent tyrosinase inhibitors. The results of the study showed that various compounds had a specific activity greater than cogic acid. I have some queries.

In the statistical analysis subsection (materials and methods) you should not only specify the program you used to calculate significance but, also the various tests performed. Please specify.

Page 2 line 55-56 you should add: "curcumin and its derivatives are already in use as an oral supplement for various medical conditions" and cite an article such as: doi: 10.1111/dth.12842. 

Thank You

Author Response

We thank the reviewer for the kind comments. All experiments were done in triplicate. All calculations were done using GraphPad Prism first for calculating IC₅₀ by fitting the experimental curve with the equation 1 mentioned in the manuscript and then standard deviation were directly calculated by the software when extrapolating the IC₅₀.

For the utilization of curcumin, the text has been amended and the references have been changed accordingly (page 2, lines 56 to 63, highlighted in yellow).

Author Response File: Author Response.pdf

Reviewer 3 Report

The manuscript from Anan Athipornchai et al., reports the investigation of tyrosinase inhibitory activity, the inhibition mechanism, and the structure-activity relationship of natural and modified curcuminoids using bot L-tyrosine and DOPA as substrates.

The topic is a matter of interest since the medical and aesthetical unfavorable impact of pigmentary disorders has prompted a constant search for new non-toxic depigmenting agents.

The introduction provides a clear background and is informative. Just a note of caution: curcumin consumption for centuries ensures safety on ingestion but does not possibly ensure its safety upon topical application (lines 56-58). I’m also aware that curcumin and its derivatives are commonly used in cosmetics and wound healing, so I’m not discussing the truth of the statement but I suggest rephrasing those lines.  

Author Response

We very much appreciate reviewer’s kind suggestions, and we agree with the reviewer’s line of reasoning. However, a number of evidences confirm that curcumin and its derivatives are safe upon topical application, and are used in commercial cosmetics and wound healing. Further discussion and references have been added. The text has been amended and the references have been changed accordingly (page 2, lines 56 to 63, highlighted in yellow).

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

The authors responded to all queries the paper is publishable.