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Article
Peer-Review Record

Antimicrobial and Anticancer Potential of Polyketides Isolated from the Caribbean Marine Sponge Plakortis halichondrioides

Drugs Drug Candidates 2025, 4(1), 6; https://doi.org/10.3390/ddc4010006
by Carlos Jiménez-Romero 1,2, Luis A. Amador 1,2, Gabriel Castro-Falcón 2 and Abimael D. Rodríguez 1,2,*
Reviewer 1: Anonymous
Reviewer 2: Anonymous
Reviewer 3:
Drugs Drug Candidates 2025, 4(1), 6; https://doi.org/10.3390/ddc4010006
Submission received: 22 January 2025 / Revised: 7 February 2025 / Accepted: 13 February 2025 / Published: 15 February 2025
(This article belongs to the Collection Chirality in Drugs and Drug Candidates)

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The current manuscript can be accepted for publication on condition that the authors respond to the following comments and inquiries. Upon receiving the authors’ response, the manuscript can be accepted for publication. (Minor revision)

1.       Could you please provide purity of compounds 1-6?

2.       The author should provide the 1H and 13C NMR spectra for compounds 3-6 in the Supporting Information.

3.       Although you mentioned in the Methods section that statistical analysis was performed, I couldn't find any statistical analysis results presented in the Results section. Could you please clarify or provide the statistical analysis results?"

4.       Why did you choose pkCSM server?

5.       In Table:3 CYP2D6 inhibitor/substrate: in this known for Chloroquine? Discuss why a no for Manadodioxan D may be beneficial

6.       What concentration of DMSO is commonly used as a vehicle control in experiments?

7.       Please make the Conclusion section shorter. Just summarize the most important results, don't repeat everything

Kind regards,

Author Response

Please see the document attached.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The manuscript "Antimicrobial and Anticancer Potential of Polyketides Isolated from the Caribbean Marine Sponge Plakortis halichondrioides" by C. Jiménez-Romero et al. is devoted to the isolation, structure elucidation and bioactivity testing of sponge-derived polyketides. The authors described 2 novel structures using NMR, HRMS and IR spectroscopy methods. All isolated compounds were tested for cytotoxic (MTS assay), antimalarial and antimycobacterial activity. Based on experimental results and ADMET predictions the manadodioxan D was identified as a promising drug candidate.

The manuscript is written well (except minor revisions highlighted below) and easy to read. Presented material could be interesting for further drug development process and search for new chemotypes across natural products. I recommend to accept presented work after minor revision.

Minor revisions needed:

1. line 29 and after: "AMES" is not an abbreviation, it's a name. First, please, use "Ames". Second, it will be better to delete this information from abstract: it's just predicted properties not approved experimentally;

2. Table 1: seco-Plakortide - seco-Plakortide (P shouldn't be itallic);

3. line 101 and after: It's not clear the designation like H2-17α - index "2" means 2 hydrogen atoms while the "17α" means just 1 from two diastereotopic atoms at C17. Please make these designations clear;

4. line 309: 2H-tetrazolium - 2H-tetrazolium;

5. line 364, Table 3: the font used in table not the same for main text. As well as it could be transferred into the supporting info.

Author Response

Please see the document attached.

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

As part of the efforts in marine natural product discovery, the manuscript describes the isolation of six compounds from the Caribbean sponge Plakortis halichondrioides: plakortilactone (1) and seco-plakortide F acid (2), manadodioxan D (3), 13-oxo-plakortide F (4), plakortide F (5) and manadodioxan E (6). Compounds 1 and 2 were new natural products while the others were previously published. The authors performed detailed structural elucidations including stereochemistry characterizations using 1D 2D NMR, HRMS, FTIR. The stereochemistry of compound 2 was established by comparison to the published structure of compound 5.

The authors further performed antimicrobial (P. falciparum, M. tuberculosis) and anticancer (DU-145, A-2058) assays for compounds 2-4. Pharmacokinetics and toxicity of compound 3 was computationally evaluated through an open-source server.

The manuscript is well-written and will provide new knowledge regarding the structure and activities of the isolated compounds. It is recommended to publish with a minor revision:

Regarding compound 2 structure elucidation, there was no correlation connecting between position 7 to position 9 in Figure 4. Please add discussions regarding if the COSY correlations (between position 7 and position 10) were missing or they were undistinguishable due to overlapping signals. It is recommended to try TOCSY NMR experiments to establish the missing signals.

Author Response

Please see the document attached.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The authors have responded to all my comments and suggestions. As such, the manuscript can be acceptable for publication in its current status.

Reviewer 2 Report

Comments and Suggestions for Authors

The revised version of the manuscript could be accepted for publication.

Please, check the references section carefully during proofreading. Some journal names are given in full form (61. Organic Chemistry Frontiers) while the most - as an abbreviation. Ref. 51: "N-Desethylchloroquine Formation" is larger than other text.

Reviewer 3 Report

Comments and Suggestions for Authors

Thank you for the reply on the structure elucidation on compound 2. My comment has been addressed.

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