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Marine Drugs
Volume 24
Issue 4
10.3390/md24040133
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Review
Peer-Review Record

Marine Pharmacology in 2022–2023: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis and Antiviral Activities, Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action

Mar. Drugs 2026, 24(4), 133; https://doi.org/10.3390/md24040133
by Alejandro M. S. Mayer 1,*, Veronica A. Mayer 2, Michelle Swanson-Mungerson 3, Marsha L. Pierce 1, Cai M. Roberts 1, Abimael D. Rodríguez 4, Fumiaki Nakamura 5 and Orazio Taglialatela-Scafati 6
Reviewer 2:
Laurent Picot
Reviewer 3: Anonymous
Mar. Drugs 2026, 24(4), 133; https://doi.org/10.3390/md24040133
Submission received: 4 February 2026 / Revised: 27 March 2026 / Accepted: 1 April 2026 / Published: 9 April 2026
(This article belongs to the Section Marine Pharmacology)

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This review exhaustively covers the marine pharmacology literature published between 2022 and 2023, consolidating data about marine natural compounds, their mechanisms of action and therapeutic potential. More than 170 compounds, isolated from sponges, algae, fungi, bacteria, corals and fish, are highlighted, showing diverse activities like anticancer, anti-inflammatory, antioxidant, antihypertensive, hypolipidaemic, and neuroprotective. Also, it includes a look at reviews on specific areas such as antimicrobials, antiprotozoals, cardiometabolic and nervous system.

However, the authors should tackle the following points:

  1. For the aaptamine derivative that inhibits CDK2 and induces G1 arrest, is there any quantitative IC₅₀ reported for CDK2, and does it correlate with the level of cell cycle arrest?
  2. The anhydrodebromoaplysiatoxin modulates mTOR/p70S6K/FoxO3a and autophagy: is there a dose-response profile that could determine a safe therapeutic window before causing cell toxicity?
  3. For ageladine A and agelasidine A, is there evidence of selectivity for endothelial cells versus tumour cells, or systemic cytotoxicity might be possible?
  4. Have the hypolipidaemic compounds been tested in human hepatocytes in vitro to confirm PPARα/γ activation is directly via receptor binding and not mediated indirectly?
  5. Xanthophyll astaxanthin and other marine antioxidants: were they compared to classical positive controls (e.g., Vitamin E or NAC) under the same oxidative stress conditions?
  6. For peptides from oysters or fish, was gastrointestinal enzymatic stability or in vivo bioavailability evaluated to support their therapeutic potential?
  7. Many alkaloids and polyketides from fungi and sponges are reported as inhibitors of pathways like PI3K/Akt, NF-κB, MAPK. Were docking or molecular modelling studies performed to confirm the binding site and affinity?
  8. For osteoclastogenesis inhibitors, is there any correlation between chemical structure and inhibitory potency to allow SAR conclusions?
  9. For compounds regulating cytosolic Ca²⁺, was the kinetics of activation/inhibition assessed and related to the chemical structure of the peptide-polyketide hybrid?
  10. Among antimicrobial compounds, are MIC or EC₅₀ reported against clinical resistant strains, and compared with reference antibiotics?
  11. For antiviral inhibitors of dengue, Zika, and COVID-19, was activity evaluated in complete viral replication models in vitro or only in isolated protein assays (like viral proteases)?
  12. For antimalarial and antiparasitic marine compounds, is there selectivity data between human cells and protozoa to minimise systemic toxicity?
  13. Hypolipidaemic and antidiabetic compounds: do preclinical assays include liver and kidney safety besides metabolic efficacy?
  14. Bryostatin-1 and astaxanthin for neuroprotection: were they compared with reference drugs in in vivo neurodegenerative models, and any data about brain bioavailability?
  15. Conotoxins and tetrodotoxin: does the review detail possible off-target effects or neurotoxicity in animal models?
  16. Enzyme inhibitors and anti-ageing peptides: are kinetic studies done to determine inhibition type (competitive, non-competitive) and Kᵢ?
  17. Use of nanotechnology for marine compound delivery: are there comparative data on bioavailability and efficacy vs free compound administration?

Finally, it is suggested authors include the following sections:

  1. Add a SAR summary table, showing structure-activity correlation and relative potency per chemical family.
  2. Include a section on pharmacokinetics and in vivo stability of the most promising bioactive compounds.
  3. Incorporate signalling pathway diagrams affected, showing compounds and effects for better visual clarity.
  4. Consider a subsection about selective toxicity, comparing normal human cells versus target cells.

Author Response

Please see attachment. Thank you. 

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Excellent review. It will be very useful for the community of Marine Drugs researchers.

Author Response

Please see attachment. Thank you. 

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

This review article comprehensively summarizes pharmacological studies on marine natural products (MNPs) published between 2022 and 2023, analyzing research conducted by groups from 40 countries to highlight recent trends and advances in marine pharmacology. A total of 173 structurally characterized compounds are included, covering a wide spectrum of biological activities such as antibacterial, antifungal, antituberculosis, antiprotozoal, antiviral, and anticancer effects, as well as anti-inflammatory, immunomodulatory, neuroprotective, and antidiabetic properties.

The manuscript also discusses the clinical development status of marine-derived drugs, underscoring the continued importance of marine organisms as valuable resources for drug discovery. Overall, this review serves as a well-organized and informative reference that captures the current landscape and future potential of marine pharmacology research.

However, there are some minor points that require attention from author as below:

  1. Please include a world map (heatmap) showing the primary collection locations of the marine organisms studied in the Introduction.
  2. Please include a pie chart in the Introduction showing the proportion of source organisms, such as sponges, soft corals, and microorganisms, to visualize which taxonomic group has been most actively studied.
  3. Add a brief paragraph after Table 1 explaining how specific functional groups influence activity.
  4. Table 1 : If cytotoxicity data against normal cells are available, be sure to mention them and include the Selectivity Index (SI).
  5. Table 1 : Compare the IC50 values with those of the standard treatments for each disease (e.g., the anticancer drug Doxorubicin, the antibiotic Vancomycin, etc.).
  6. It would be very useful to include a graph showing the yearly trends of terpenoids, alkaloids, polyketides, and other compounds categorized by structural features, before the start of Section 2.1. Antibacterial and Antituberculosis Activity.
  7. Add a brief paragraph after Table 2 explaining how specific functional groups influence activity.
  8. Table 2 : If cytotoxicity data against normal cells are available, be sure to mention them and include the Selectivity Index (SI).
  9. Table 2 : Compare the IC50 values with the positive control.
  10. Including a schematic at the end of Section 3.2, Anti-Inflammatory Activity, showing how key compounds inhibit or activate specific intracellular signaling pathways would greatly enhance the value of the manuscript.
  11. Including a schematic at the end of Section 3.4, Marine Compounds Affecting the Nervous System, showing how key compounds inhibit or activate specific intracellular signaling pathways would greatly enhance the value of the manuscript.
  12. In Section 3.4, Although some comparisons with Donepezil are mentioned, most comparisons with other compounds are lacking; therefore, please compare the IC50 values.
  13. Add a brief paragraph after Table 3 explaining how specific functional groups influence activity.
  14. Table 3 : If cytotoxicity data against normal cells are available, be sure to mention them and include the Selectivity Index (SI).
  15. In the Conclusions, address the chronic 'supply issue' in the field of marine natural products and mention whether aquaculture or total synthesis studies are being conducted to overcome this challenge.
  16. In the Conclusions, suggesting how cutting-edge technologies, such as AI-based drug discovery and Antibody-Drug Conjugates (ADCs), could be applied to marine natural product research would enhance the timeliness and relevance of the manuscript.
  17. Page 3, Line 86 : ‘MRSA’ is written in italics in the table.
  18. Page 3, Line 86 : ‘MSSA’ is written in italics in the table.
  19. Page 3, Line 87 : Please add a period after “S.”
  20. Page 3, Line 87 : Please write Trypanosoma in italics.
  21. Page 7, Line 97 : Why was italics used?
  22. Page 8, Line 150 : Please write in vitro in italics.
  23. Page 9, Line 208 : Why was italics used?
  24. Page 9, Line 210 : Please remove the italics.
  25. Page 9, Line 214 : Please revise it to “At 0.53 mM,”.
  26. Page 10, Line 236 : Why was italics used?
  27. Page 11, Line 273 : Why was italics used?
  28. Page 11, Line 278 : Please change the number in “(34)” to bold.
  29. Page 11, Line 279 : Please write Aspergillus fumigatus in italics.
  30. Page 11, Line 280 : Please write in vitro in italics.
  31. Page 11, Line 282 : The closing parenthesis is missing. Please add it.
  32. Page 11, Line 284 : Please change the number in “(41)” to bold.
  33. Page 11, Line 285 : Please write Aspergillus fumigatus in italics.
  34. Page 11, Line 288 : Please change the number in “(43)” to bold.
  35. Page 11, Line 289 : Please write Duva florida in italics.
  36. Page 11, Line 293 : Please change the number in “(36)” to bold.
  37. Page 11, Line 293 : Please write Ishige okamurae in italics.
  38. Page 11, Line 294 : Please write Ecklonia cava in italics.
  39. Page 11, Line 298 : Please change the number in “(42)” to bold.
  40. Page 11, Line 299 : Please write Dactylospongia elegans in italics.
  41. Page 11, Line 305 : Please change the number in “(39)” to bold.
  42. Page 11, Line 306 : Please change the number in “(39)” to bold.
  43. Page 12, Table 2, the 7th row, 4th column : Please write in vitro in italics.
  44. Page 12, Table 2, the 11th row, 5th column : Please revise it to “6.03 mg/mL.”
  45. Page 14, Table 2, the 22th row, 6th column : Please write in vivo in italics.
  46. Page 20, Line 394 : Why was italics used?
  47. Page 21, Line 435 : Why was italics used?
  48. Page 21, Line 442 : Please revise it to “interleukin-6.”
  49. Page 21, Line 443 : [number] : Reference / (bold number) : Metabolites
  50. Page 21, Line 445 : [number] : Reference / (bold number) : Metabolites
  51. Page 21, Line 449 : [number] : Reference / (bold number) : Metabolites
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  82. Page 23, Line 561 : [number] : Reference / (bold number) : Metabolites
  83. Page 23, Line 565 : Why was italics used?
  84. Page 24, Line 570 : [number] : Reference / (bold number) : Metabolites
  85. Page 24, Line 575 : [number] : Reference / (bold number) : Metabolites
  86. Page 24, Line 578 : [number] : Reference / (bold number) : Metabolites
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  89. Page 24, Line 593 : Why was italics used?
  90. Page 24, Line 594 : Why was italics used?
  91. Page 24, Line 600 : Please check whether the text color is different.
  92. Page 25, Line 620 : Please revise it to “Aβ peptides.”
  93. Page 25, Line 631 : Please revise it to “Aβ peptides.”
  94. Page 25, Line 641 : Please revise it to “butyrolactone.”
  95. Page 25, Line 642 : Please revise it to “amelioration.”
  96. Page 25, Line 657 : Please revise it to “activity.”
  97. Page 25, Line 662 : Please check whether the text color is different.
  98. Page 25, Line 664 : Please check whether the text color is different.
  99. Page 25, Line 670 : Please check whether the text color is different.
  100. Page 26, Line 682 : Please check whether the text color is different.
  101. Page 26, Line 692 : Please check whether the text color is different.
  102. Page 27, Line 737 : Please revise it to “spontaneous.”
  103. Page 28, Table 3, the 6th row, 5th column : Please revise it to “PPAR-α.”
  104. Page 28, Table 3, the 10th row, 5th column : Please revise it to “PPAR-γ.”
  105. Page 28, Table 3, the 13th row, 4th column : Please add a space before “17.”
  106. Page 28, Table 3, the 16th row, 5th column : Please revise it to “PPAR-γ.”
  107. Page 28, Table 3, the 18th row, 5th column : Please revise it to “PPAR-γ.”
  108. Page 28, Table 3, the 21th row, 4th column : Please add a space before “41.”
  109. Page 29, Table 3, the 10th row, 3th column : Please revise it to “dysfunction.”
  110. Page 30, Table 3, the 8th row, 4th column : lease add a space before “40.”
  111. Page 30, Table 3, the 8th row, 4th column : Please revise it to “PPAR-α.”
  112. Page 31 : Please remove the italics from the names of compounds 115 and 116 below.
  113. Page 36, Line 822 : Please revise it to “suberitoides.”
  114. Page 36, Line 833 : Please revise it to “PPAR-α.”
  115. Page 36, Line 846 : Please revise it to “as well as.”
  116. Page 36, Line 860 : Please revise it to “PPAR-γ.”
  117. Page 36, Line 865 : Please revise it to “PPAR-γ.”
  118. Page 37, Line 905 : Please revise it to “NFATc1 signaling.”
  119. Page 37, Line 906 : Please revise it so that the paragraph is not split.
  120. Page 37, Line 907 : Please revise it to “dysfunction.”
  121. Page 37, Line 914 : Please revise it to “Lissoclinum.”
  122. Page 38, Line 952 : Please revise it to “IκB.”
  123. Page 39, Line 980 : Please revise it to “PPAR-γ.”
  124. Page 39, Line 984 : Research fields are not written in italics.
  125. Page 39, Line 997 : Please revise it to “saponins.”
  126. Page 39, Line 1013 : Please revise it to “(d).”
  127. Page 40, Line 1036 : Please revise it to “metalloaminopeptidases.”
  128. Page 40, Line 1045 : Why was italics used?
  129. Page 40, Line 1046 : Please add a period.
  130. Page 40, Line 1056 : Why was italics used?
  131. Page 40, Line 1057 : Why was italics used?
  132. Page 40, Line 1061 : Why was italics used?
  133. Page 42, Line 1163 : Please write in vitro in italics.
  134. Page 43, Line 1217 : Please write in vitro in italics.
  135. Page 43, Line 1217 : Please write in silico in italics.
  136. Page 44, Line 1233 : Please write in vitro in italics.
  137. Page 44, Line 1233 : Please write in silico in italics.
  138. Page 44, Line 1240 : format standardization
  139. Page 49, Line 1479 : Please write in vivo in italics.
  140. Page 50, Line 1537 : Please write in vitro in italics.

Author Response

Please see attachment. Thank you. 

Author Response File: Author Response.pdf

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