Synthesis and Anti-Inflammatory Activity of (Z)-4-(2-(3-Oxopiperazin-2-ylidene)acetyl)benzoic Acid

Round 1

Reviewer 1 Report

This is an interesting and well-written paper that fits nicely into the remit of Molbank. Three new organic compounds are prepared and fully characterised and in addition two X-ray structures are determined. The anti-inflammatory activity of the key compound is also assessed. It can be accepted for publication once the following mostly minor suggestions are attended to:

1. For completeness, the experimental procedure for isolation of cpd 1 should be included in the Materials and Methods section, i.e. the procedure corresponding to Scheme 1.

2. The two X-ray structures reported show both intra- and intermolecular hydrogen bonding which is of interest and merits a mention. Extra diagrams showing the hydrogen-bonded dimers formed by "piron" and the extended network structure formed by cpd 3 hydrate would be of interest to readers and also perhaps of some relevance to the biological activity.

3. It would be relevant for the authors to comment on how the anti-inflammatory activity of cpd 1 discussed in section 2.2 compares with that of 'piron'.

4. For reference 11, the 'article number' (MR000034) should be given as part of the reference (in addition to appearing in the DOI).

5. The table of contents for the supplementary materials can be improved. Replace 3 by S3 and 4 by S4–S10.

Author Response

Reviewer #1: This is an interesting and well-written paper that fits nicely into the remit of Molbank. Three new organic compounds are prepared and fully characterised and in addition two X-ray structures are determined. The anti-inflammatory activity of the key compound is also assessed. It can be accepted for publication once the following mostly minor suggestions are attended to:

1. For completeness, the experimental procedure for isolation of cpd 1 should be included in the Materials and Methods section, i.e. the procedure corresponding to Scheme 1.

Response:

We added this information in the manuscript.

2. The two X-ray structures reported show both intra- and intermolecular hydrogen bonding which is of interest and merits a mention. Extra diagrams showing the hydrogen-bonded dimers formed by "piron" and the extended network structure formed by cpd 3 hydrate would be of interest to readers and also perhaps of some relevance to the biological activity.

Response:

We added additional information about X-ray structures in the manuscript.

3. It would be relevant for the authors to comment on how the anti-inflammatory activity of cpd 1 discussed in section 2.2 compares with that of 'piron'.

Response:

We added this information in the manuscript.

4. For reference 11, the 'article number' (MR000034) should be given as part of the reference (in addition to appearing in the DOI).

Response:

We fixed this issue.

5. The table of contents for the supplementary materials can be improved. Replace 3 by S3 and 4 by S4–S10.

Response:

All numbers of figures and tables in the table of content for the supplementary materials contain the required letter “S”.

Reviewer 2 Report

Manuscript Number: molbank-2801958

The manuscript of M.V. Dmitriev, E.E. Khramtsova , D.Y. Apushkin, A.I. Andreev, I. I. Kovalenko, I.V. Mashevskaya, A.N. Maslivets “Synthesis and Anti-inflammatory Activity of (Z)-4-(2-(3-Oxopiperazin-2-ylidene)acetyl)benzoic acid” presents the synthesis of (Z)-4-(2-(3-oxopiperazin-2-ylidene)acetyl)benzoic acid as the metabolite of (Z)-3-(2-oxo-2-(p-tolyl)ethylidene)piperazin-2-one. And studies of anti-inflammatory activity of the synthesized metabolite in vivo.  

The submitted manuscript meets the conditions of Molbank for Communication papers. According Scifinder the target compound and numbered intermediates are new compounds. Authors provide sufficient characterisation for them including x –ray diffraction analysis for 2 compounds.

However, some issues needed to be added and addressed before publication of it.

1.      The main concern: The authors report in vivo experiments, but there is no information on ethical issues, such as local permissions. Please provide it.

2.      Please use the same style points through all text. Line 26 is it necessary to mention the name of compound twice? You have it also in the legend. Perhaps biological activities can be also deleted.

Consequently, I do recommend accepting this manuscript for publication with major revision.

Author Response

Reviewer #2: The manuscript of M.V. Dmitriev, E.E. Khramtsova , D.Y. Apushkin, A.I. Andreev, I. I. Kovalenko, I.V. Mashevskaya, A.N. Maslivets “Synthesis and Anti-inflammatory Activity of (Z)-4-(2-(3-Oxopiperazin-2-ylidene)acetyl)benzoic acid” presents the synthesis of (Z)-4-(2-(3-oxopiperazin-2-ylidene)acetyl)benzoic acid as the metabolite of (Z)-3-(2-oxo-2-(p-tolyl)ethylidene)piperazin-2-one. And studies of anti-inflammatory activity of the synthesized metabolite in vivo.  

The submitted manuscript meets the conditions of Molbank for Communication papers. According Scifinder the target compound and numbered intermediates are new compounds. Authors provide sufficient characterisation for them including x –ray diffraction analysis for 2 compounds.

However, some issues needed to be added and addressed before publication of it.

1. The main concern: The authors report in vivo experiments, but there is no information on ethical issues, such as local permissions. Please provide it.

Response:

We added this information in the manuscript.

2. Please use the same style points through all text. Line 26 is it necessary to mention the name of compound twice? You have it also in the legend. Perhaps biological activities can be also deleted.

Response:

The whole manuscript is written in the same style. Please provide more specific examples of errors in style.

We believe that a little duplication of information in this case (line 26) may make the article clearer.

Consequently, I do recommend accepting this manuscript for publication with major revision.

Reviewer 3 Report

he submitted manuscript is devoted to the synthesis and anti-inflammatory activity of (Z)-4-(2-(3-oxopiperazin-2-ylidene)acetyl)benzoic acid. The research seems to have been carefully done, but the authors need to elaborate on their discussion before publishing it in the Molbank. This part of the manuscript is very short compared to the experimental section, and the research results are practically not discussed. The authors received two structures that could be briefly described (in particular hydrogen bonds). There are a few editorial errors that should also be corrected.

Minor editing of English language required

Author Response

Reviewer #3: The submitted manuscript is devoted to the synthesis and anti-inflammatory activity of (Z)-4-(2-(3-oxopiperazin-2-ylidene)acetyl)benzoic acid. The research seems to have been carefully done, but the authors need to elaborate on their discussion before publishing it in the Molbank. This part of the manuscript is very short compared to the experimental section, and the research results are practically not discussed. The authors received two structures that could be briefly described (in particular hydrogen bonds). There are a few editorial errors that should also be corrected.

Response:

We added additional information about X-ray structures and biological assay in the discussion.

Round 2

Reviewer 2 Report

 Accept in present form

Reviewer 3 Report

My comments have been taken into account and the manuscript can be published in the Molbank.