PONE-D-21-21460

Antitubercular activity assessment of fluorinated chalcones, 2‐aminopyridine‐3‐carbonitrile and 2‐amino-4H-pyran‐3‐carbonitrile derivatives: In vitro, molecular docking and in-silico drug likeliness studies

PLOS ONE

Dear Dr. Shaik,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Oct 17 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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We look forward to receiving your revised manuscript.

Kind regards,

Hanna Landenmark

Associate Editor, PLOS ONE

on behalf of 

Pooja Chawla

Academic Editor, PLOS ONE

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Additional Editor Comments (if provided):

Authors have done good work. Although the synthetic part has already been published, the antitubercular activity was carried out. The work could have been substantiated with enzymatic studies. But in my opinion this much work may be published.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: N/A

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors have presented antitubercular actvities for the previously reported compounds.

1. Introduction section mentions about the WHO date. Please cite the same in references.

2. Docking images are not legible. Especially, the compouds are not legible in the docking images.

3. Did the authors perform acute cytotoxicity and in vivo analysis?

4. The authors must discuss the previously performed activity of the test compounds that encouraged the appraisal of their antitubercular activity in the present report.

5. Is the clogP evaluated experimentally or theoretically? Please mention the percentage error in either case.

6. Since molecular docking forms the only basis of supporting studies, it should be discussed in details for atleast the most active compounds and corroborated with the SAR analysis.

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6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Parteek Prasher

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PONE-D-21-21460R1Antitubercular activity assessment of fluorinated chalcones, 2‐aminopyridine‐3‐carbonitrile and 2‐amino-4H-pyran‐3‐carbonitrile derivatives: In vitro, molecular docking and in-silico drug likeliness studiesPLOS ONE

Dear Dr. Shaik,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Mar 19 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Mohammad Shahid, Ph.D.

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The author have presented the anti tubercular potency of fluorinated chalcones, 2‐ aminopyridine‐ 3‐ carbonitrile and

2‐ amino-4H-pyran‐ 3‐ carbonitrile derivatives. The molecular docking and in vitro studies support the biological activity of these molecules. The authors must address the following points to improve the manuscript1.

1. The introduction section has many claims regarding the morbidity and mortality rate of TB without a valid reference. Even if the WHO statistics are cited, URL must be provided so that the readers benefit form it.

2. If the synthesis protocol is novel, the percentage yield of the compounds must be reported.

3. Drug likeliness is calculated by an online tool. Is there an ecperimental validation to the reported clogP values?

4. Is the reported online tool for calculating clogP a valid tool for thes studies? What is the incidence of error?

5. Which docking tool is used for the studies? The docking data only shows hydrogen bonding interactions. Can the other interactions of molecules with peptide be rejected?

Reviewer #2: Journal- PLOS ONE

Manuscript ID- PONE-D-21-21460R1

Title-" Antitubercular activity assessment of fluorinated chalcones, 2‐aminopyridine‐3‐

carbonitrile and 2‐amino-4H-pyran‐3‐carbonitrile derivatives: In vitro, molecular docking and in-silico drug likeliness studies"

Authors have fulfilled all the queries/comments that was asked reviewers previously. Hence, now the manuscript is well written. I believe that it is a nice piece of work for being published in the PLOS ONE. Finally, I recommend that the paper should be accepted for the publication in the present form with some justification or corrections.

Decision- Accept

Reviewer comments

1. Mention the full name NIH and PZA in the text?

2. The author mentions in the text that, the docking conformation of compound 40 “showed” good interactions and so on. This is the modelling study, thus “suggests” is the right verb to be used.

3. In docking study authors are also required to mention in what range bond distance of hydrophobic and hydrogen interactions are determined.

4. In conclusion author mentions compound 27 for the docking study while they performed docking with 26 and 40.

5. The authors need to give some more methological data regarding their analyses as how big or small was the box that the authors used for the molecular docking? Did that cube cover the whole protein or only the binding site? These information need to be provide in methodology.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Parteek Prasher

Reviewer #2: Yes: Mantasha Idrisi,

National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, MS38677,USA

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Antitubercular activity assessment of fluorinated chalcones, 2‐aminopyridine‐3‐carbonitrile and 2‐amino-4H-pyran‐3‐carbonitrile derivatives: In vitro, molecular docking and in-silico drug likeliness studies

PONE-D-21-21460R2

Dear Dr. Shaik,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Mohammad Shahid, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: