Opportunities and Difficulties in the Repurposing of HDAC Inhibitors as Antiparasitic Agents
, Prashant Tiwari 4,* and Dileep Kumar 3,*Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsJournal: Drugs and Drug Candidates
Manuscript ID: ddc-2762934
Reviewers Comments – Summary
The work is interesting and has potential, however, in its current form is not suitable for publication in Drugs and Drug Candidates. I have provided some comments for consideration.
Comments for author File: 
Comments.pdf
Some moderate editing of English language required.
Author Response
The point-wise reply to comments is attached.
Author Response File: 
Author Response.docx
Reviewer 2 Report
Comments and Suggestions for AuthorsThe review summarizes the role of HDAC and HDAc inhibitors in the treatment of parasite infections. The review in well organized and includes a deep description of the field bibliography. However a figure about HDAC mechanism of actions at the begining of the review would be informative.
Minor points:
- line 155. Change HDCA to HDAC
- line 157. histone acetiltransferase must start with capital letter
Author Response
The point-wise reply to comments is attached.
Author Response File: Author Response.docx
Reviewer 3 Report
Comments and Suggestions for AuthorsReview for the
Manuscript ID: ddc-2762934 (DDC (ISSN 2813-2998))
Type: Review
Title:
Opportunities and Difficulties in the Repurposing of HDAC Inhibitors as Anti-Parasitic Agents
Authors
Tapas Kumar Mohapatra, Reena Rani Nayak , Ankit Ganeshpurkar, Prashant Tiwari , Dileep Kumar*
Current extensive manuscript (34 pages, 178 refs.) is dedicated to the detailed review of HDAC inhibitors re-purposing, targeting the wide spectrum of parasitic diseases.
Presented review can be useful and recommended for many researchers, including pharmaceutical specialists and medicinal chemists working with antiparasitical drugs.
This review also focuses on repurposing opportunities and challenges of HDAC inhibitors that are preceded by their clinical development as potent new anti-parasitic drugs.
Despite that some review papers are already previously published (for example:
Digest paper „Klug, D.M.; Gelb, M.H.; Pollastri, M.P. Repurposing strategies for tropical disease drug discovery. Bioorg. Med. Chem. Lett. 2016, 26, 2569-2576.“ https://doi.org/10.1016/j.bmcl.2016.03.103 .
and „Ghazy, E.; Abdelsalam, M.; Robaa, D.; Pierce, R.J.; Sippl, W. Histone deacetylase (HDAC) inhibitors for the treatment of schistosomiasis. Pharmaceuticals, 2022, 15(1), 80.‘‘ https://doi.org/10.3390/ph15010080
they are mainly covering only progress in the areas dedicated for one or another specific parasitic disease and suffered from the complete, wide and more detailed view, presented in this manuscript.
The manuscript is submitted to the Section „Medicinal Chemistry and Preliminary Screening“ and the
Topical Collection: „Anti-Parasite Drug Discovery“ , thus, this submission is according to the thematic covered by this Section.
In general, current paper is clearly written, detailed, and mostly accepable in technical qualilty and language, however it still need a lot of minor corrections for the improvement of the main text and in some Figures, and also general improvement of all references part, according to the requirements for the MDPI journals.
List of recommended corrections and improvements are presented in attachment as PDF file.
When all these mentioned minor corrections and improvements will be done,
the manuscript can be accepted.
Comments for author File: Comments.pdf
Author Response
The point-wise reply to comments is attached.
Author Response File: Author Response.docx
Reviewer 4 Report
Comments and Suggestions for AuthorsHere are my comments regarding this manuscript:
Line 23 – Thus is in capital letters, change
Line 33 – Parasitic disease – change in plural (and the rest of the text accordingly) – this is not just one disease
Line 37 – this sentence needs to be replaced „Annually, one million deaths occur due to parasitic diseases.”
Line 49 – change the sencence, it is grammatically incorrect
Line 209 – correct typo
Line 239 – change tgHDAC into TgHDAC
Figure 2. – Text missing below acetylated proteins
Line 350 – how was apicidin used as antimalarial, the way that I’s presented in the manuscript implies that it was used in humans, it should be more clearly stated what it means in this sentence
Line 366 – why is Apicidin written with a capital letter?
Line 372 – typo in the figure title
Figure 3 – hydroxamic acid derivatives are placed together with carboxylic acids, they should be separatedin two groups as it is in the text
Lines 398 and 399 – IC50 is written differently in the text, check in the entire manuscript
Line 410 – this sentence needs to be improved, “compounds of hydroxamic acid” sounds strange, zinc binding group is also hydroxamic acid so here it sounds as if it doesn’t belong to this group of compounds
Line 511 – Table 1 – in the text describing this table is placed that it contains chemical structure which implies that it contains image of the structure, please correct
Line 508 and 509 – compounds numbers in bold (and check in the entire manuscript)
Figure 5 – compound 34 is not hydroxamic acid, and please correct its structure, some atoms overlap. Why are there hydroxamic acids separated from the ones that were listed in the figure 3, but there they were marked as carboxylic acid derivatives?
Figure 6 – again here are some structures that belong to the hydroxamic acid group, I strongly suggest to the authors to revise the division of all the compounds they mention in the manuscript
Line 667 and 668 – which compounds do you mean here? Which are those two recently approved hydroxamates?
Line 711 and 729 – the term antileishmanial is written differently, please check the entire manuscript that all terms are written equally.
Line 875 – please correct this sentence
Comments on the Quality of English LanguageI've noticed several grammar mistakes in the manuscript, so I advise you to revise the manuscript regarding the language
Author Response
The point-wise reply to comments is attached.
Author Response File: Author Response.docx
