Synthesis and In Vitro Antitumor Activity Evaluation of Gefitinib-1,2,3-Triazole Derivatives
Dirk Schepmann
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThe manuscript entitled “Synthesis and in vitro antitumor activity evaluation of gefitinib-1,2,3-triazole derivatives” (Manuscript ID: Molecules-2833727) by Li et al. describes the synthesis of gefitinib 1,2,3-triazole derivatives. The derivatives were characterized and evaluated for anti-tumor activity. However, the manuscript needs major changes before making the decision.
1. Authors can provide reaction conditions and yields on the Scheme. Figure 4 should be replaced as Scheme 1.
2. Authors should include the IC50 of the compounds on the normal human cell lines.
3. Authors can provide the details of half maximal inhibitory concentrations, is it the mean of 3 experiments, details of cell lines? Provide the details in the legend of Table 1.
4. Reason for choosing H1299 cells, when 4b exhibited good activity of 1.56±0.06 in NCI-H1437 cells for studying apoptosis?
5. Authors should provide an inset for DAPI staining figures to show the typical apoptotic features.
6. Why was clonogenic assay performed at concentrations lower than IC50 values, and explain how there is 80% inhibition rate in colony formation for both the compounds?
7. Did authors consider any target-based studies or any computational studies?
8. Why was dose dependency studied in different concentrations for different assays? Fig 6 (2,4,8), Fig 7 (1,2,4), Fig 8 (4,8,16) µM?
9. Fig 7 legend says 4a or 4b? Is this 4a and 4b?
10. All references need attention for uniformity and according to the journal specifications.
11. Minor corrections like italicizing the scientific names, spacing errors, spelling mistakes need to be corrected in the entire manuscript.
Comments on the Quality of English Language
None
Author Response
Dear Reviewer: Thank you very much for taking the time to review this manuscript. We have revised our manuscript based on your suggestions and instructions and carefully considered your comments. Attached please find a point-by-point response to all of the questions raised by the reviewer.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
Comments and Suggestions for AuthorsThe manuscript describes the synthesis and biological evaluation of 14 gefitinib triazole derivatives, with focus on antitumor activity on lung cancer cell lines.
The chemistry is straight-forward and is yet another example of what can be done with click-chemistry. The structural diversity of the synthesized compounds is therefore a bit limited, though.
The introduction could need some improvement. The numbering of compounds is confusing because in Figure 2 the same codes (4a-4i and 4a-z) have been used as for the synthesized compounds which are presented in the paper (4a-4n). Basically, the number 4 has been used for 3 different type of compounds. The manuscript would benefit from using different numbers for the examples of triazole derivatives mentioned in the introduction, so that the numbering of the synthesized compounds can remain as it is.
The presentation of the biological data is ok, but the inhibition of the positive control (Gefitinib) should be added to table 1.
While the identity of the compounds has been confirmed by NMR and HRMS, I couldn't find any data regarding the purity of the compounds. This is in important aspect when conducting biological assays. Are their any data available (elemental analysis, HPLC?)
Small findings in the experimental section:
- The brand / name of the cell incubator is missing
- on page 13, the sentence "After the plates were air-dry, taking a picture." should be rephrased into proper english.
- the term "Image J" was frequently used but is not specified further - is it an instrument or software?
Author Response
Dear Reviewer: We would like to thank the reviewer for excellent comments, as well as the revised manuscript has been significantly improved. According to Reviewers’ recommendations, we have revised our manuscript carefully, and all amendments are highlighted in yellow in the revised manuscript. Attached please find a point-by-point response to all of the questions raised by the reviewer.
Author Response File: Author Response.pdf
Reviewer 3 Report
Comments and Suggestions for AuthorsThe paper reported some me-too compounds with anti-cancer activity. The paper should be major revision.
1. The key intermediate and final compounds are solid, so the authors need to give the melting point for all compounds.
2. Some of the 13C NMR data are wrong, the author should be reanalysis.
3. Whether the target protein is known? If known, you should test the enzyme activity and the molecular simulation.
4. Some references are wrong, especially for the author name.
Comments on the Quality of English LanguageSome sentences should be revised.
Author Response
Dear reviewer: We would like to thank the reviewer for providing us with the valuable comments and feedback on our research. After carefully reading and considering all comments provided, we have amended our manuscript accordingly. In addition, the amendments are highlighted in the revised manuscript. Attached please find a point-by-point response to all of the questions raised by the reviewers.
Author Response File: Author Response.pdf
Round 2
Reviewer 1 Report
Comments and Suggestions for AuthorsInclude the full form of NC in all the figure legends, wherever appropriate.
Comments on the Quality of English LanguageNone
Reviewer 3 Report
Comments and Suggestions for AuthorsAccept
