Synthesis and Biological Activities of Some Metal Complexes of 2-Thiouracil and Its Derivatives: A Review

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Comments for author File: Comments.pdf

Comments on the Quality of English Language

Moderate editing of English language required

Author Response

Manuscript title: “Synthesis and Biological activities of some metal complexes of 2-thiouracil and its derivatives: a review”,

authors: Petja Marinova, Kristina Tamahkyarova

Dear Reviewer 1,

Thank you very much for your helpful review. We have accepted all your remarks and the text is properly changed.

Our comments (highlighted in red) are as follows:

Main concerns:

1. In the first part, the authors listed a lot of metal can form complexes with 2-thiouracil and its derivatives. However, the authors should provide in-depth analysis of these compounds. They should analysis the structure difference when 2-thiouracil coordinate with different metals. And spectrophotometric or X-ray difference analysis should also be provided when substitutions happens at 2-thiouracil.

We added table 1 (382-384) and figure 7-28 for in-depth analysis of metal complexes.

2. When the authors summarize the biological functions of metal complexes 2-thiouracil, they failed to provide the mechanism of these compounds. what’s the target proteins of these complexes in bacteria, fungi and cancer cells? What’s the possible biological processes could be affected after treating with metal complexes. More importantly, they should also analyze the structure-reactivity relationship when different metals or substitutions happen to the complex analogues.

We added figure 29 and table 2, 3 and 4 for summarize the biological activities of these compounds.

3. There also some problems with the structure of the manuscript. A lot paragraphs are just one sentence or two. Some same subjects are divided into multiple paragraphs.

We fixed this issue in the revised manuscript.

Minor points:

1.Paragraph 2 and 3 should be combined, both are talking about the function of thiouracil analogues on thyroid gland.

Done. We combined paragraph 2 and 3.

2. Line 40, they authors should use surname when they cite somebody’s work.

Done. We deleted the first name of the authors.

3. In line 50, figure1 is redundant. Same thing happens to line 59 and line 65.

We deleted line 50, 59 and 65.

4. Line393, the full name of 5FU should be annotated.

We added the full name of the compound.

5. Line 401 and line 407 are almost identical.

We rephrased first paragraph (486-488 in revised manuscript).

6. Line 424, it should be 2-thiouracil.

We added “h” in the name of ligand.

The corrections in the paper have been made in accordance with the reviewer’s remarks.

Reviewer 2 Report

Comments and Suggestions for Authors

Unfortunately, I cannot recommend the review for publication in the journal Compounds in its present form.

There are significant comments that require improvement.

1. The introduction is very sparse and mainly concerns the biological activity of pyrimidines for the treatment of the thyroid gland. It is strongly recommended to expand the introduction and refer to reviews regarding the biological activity of pyrimidine derivatives. For example, https://doi.org/10.1016/j.heliyon.2023.e16773; https://doi.org/10.1007/s11172-019-2686-x; https://doi.org/10.1186/s43094-021-00274-8, etc.

2. The description of complexes of uracil, 2-thiouracil and their derivatives is not informative. It is necessary to add corresponding drawings for each complexes.

3. In addition, since the review concerns biological activity, it would be more convenient and logical to make a summary table that would describe the compound, the type of activity and its quantitative characteristics.

Comments on the Quality of English Language

Minor editing of English language required.

Author Response

Manuscript title: “Synthesis and Biological activities of some metal complexes of 2-thiouracil and its derivatives: a review”, 

authors: Petja Marinova, Kristina Tamahkyarova

Dear Reviewer 2,

 

Thank you very much for your helpful review. We have accepted all your remarks and the text is properly changed.

 

Our comments (highlighted in red) are as follows:

 

Unfortunately, I cannot recommend the review for publication in the journal Compounds in its present form.

There are significant comments that require improvement.

1.The introduction is very sparse and mainly concerns the biological activity of pyrimidines for the treatment of the thyroid gland. It is strongly recommended to expand the introduction and refer to reviews regarding the biological activity of pyrimidine derivatives. For example, https://doi.org/10.1016/j.heliyon.2023.e16773; https://doi.org/10.1007/s11172-019-2686-x; https://doi.org/10.1186/s43094-021-00274-8, etc.

We added the cited papers in the introduction part and articles with doi: 10.3389/fchem.2021.695628; https://doi.org/ 10.3390/ijms22083825.

We added scheme 1 in the introduction.

2. The description of complexes of uracil, 2-thiouracil and their derivatives is not informative. It is necessary to add corresponding drawings for each complexes.

We added figure 7-28.

Some of the articles don’t have structure. For example,

Ref. 16. DOI: 10.1007/s10953-006-9017-1;

Ref. 17. DOI: 10.1155/MBD.2002.337;

Ref. 22. DOI: 10.1016/S0277-5387(00)87013-8;

Ref. 23. Gupta, M.; Srivastava, M. N. Bull Chem. Soc. Fr. 1991, 128, 859;

Ref.24. Gupta, M.; Srivastava, M. N. Bull. Pol. Acad. Sci. 1992, 40, 1.

Ref. 25. DOI: 10.1016/0162-0134(90)85005-H;

Ref. 26.           DOI: 10.1134/S1070363222080278;

Ref. 28. DOI: 10.1016/0040-6031(92)85119-G;

Others cannot be copied or drawn. For example, (original fail)

Ref. 33.           DOI: 10.1021/ic990758n (X-ray);

Ref. 38.           DOI: 10.1016/j.jinorgbio.2005.05.003 (X-ray);

Ref. 41. DOI: 10.1016/j.saa.2012.05.085 (X-ray);

Ref. 45.           DOI: 10.1039/C9DT04423J (X-ray);

 Ref. 46.          DOI: 10.1021/ja00306a028 (X-ray);

Ref. 47.           DOI: 10.1016/S0020-1693(00)80425-9 (X-ray);

3. In addition, since the review concerns biological activity, it would be more convenient and logical to make a summary table that would describe the compound, the type of activity and its quantitative characteristics.

We added summary table with biological activity of free ligands and their metal complexes. See table 2, 3 and 4 (line 401-403; 426-428; 470-473) in revised manuscript.

 

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The authors solved most of questions. But there are still some major concerns about the revised manuscript. 1. there are still a lot paragraphs are too short, only several sentences. For example, when they talk about the Antifungi Activity, they should add more examples. 

2. The authors still did not discussed the mechanism of action in the revised manuscript. 

Comments on the Quality of English Language

Minor editing of English language is required. 

Author Response

Manuscript title: “Synthesis and Biological activities of some metal complexes of 2-thiouracil and its derivatives: a review”, 

authors: Petja Marinova, Kristina Tamahkyarova

Dear Reviewer 1,

 

Thank you very much for your helpful review.

Our comments (highlighted in red) are as follows:

 

The authors solved most of questions. But there are still some major concerns about the revised manuscript. 1. there are still a lot paragraphs are too short, only several sentences. For example, when they talk about the Antifungi Activity, they should add more examples.

 

We added ref. [54-59] in part Antifungal Activity.

 

2. The authors still did not discussed the mechanism of action in the revised manuscript.

We added ref. [60] and text (line 667-740).  

 

 

Reviewer 2 Report

Comments and Suggestions for Authors

Authors have carefully checked and modified this manuscript. Now it can be accepted for publication in this journal without further revision.

Comments on the Quality of English Language

Minor editing of English language required.

Author Response

Manuscript title: “Synthesis and Biological activities of some metal complexes of 2-thiouracil and its derivatives: a review”, 

authors: Petja Marinova, Kristina Tamahkyarova

Dear Reviewer 2,

 

Thank you very much for your helpful review.