Metal Complexes with Hydroxyflavones: A Study of Anticancer and Antimicrobial Activities

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

In this review Živković et.al, summarized transition metal complexes of biologically relevant hydroxyflavones (OH–F) ligands reported over the past 15 years. They discussed synthetic approaches and structural characterization, with a particular emphasis on coordination modes such as maltol-type, acetylacetonate-type, catechol-type, and others. They discussed anticancer and antimicrobial properties and highlighted therapeutic potentials of these complexes. The authors suggested future directions for the development of hydroxyflavones based metal complexes in terms of accuracy, reproducibility, and relevance for biological studies. This review thoroughly examined transition metal complexes with hydroxyflavones (OH-F) and provided valuable insights into the synthesis characterization and cytotoxicity or antimicrobial effects and finally suggested valuable points for the improvement of this area of research. This reviewer suggests its publication in inorganics after the following minor changes.

• Page 8: "chelation theory" reference 39" could be replaced or added with more suitable references or the references cited inside 39.
• Several references given below the figures do not belong to the structures displayed so all figures and references given in captions should be double checked e.g. below;

1. Page 7, Figure 6, references cited references 33-35 are not corresponding to the structures displayed.
2. Page 29, Figure 17, reference 34 is wrongly cited
3. Page 32 Figure 18, reference 32 does not belong to the structure, does the author mean 33, 34?

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Reviewer 2 Report

Comments and Suggestions for Authors

This review summarises advancements from the past 15 years in the synthesis and characterization of metal-based compounds bearing hydroxyflavone ligands. It deals with various coordination modes and related structural details. The ms also summarizes biological testing results, with a focus on anticancer and antimicrobial applications. From these studies it emrges the therapeutic potential of the complexes. The authors also discuss current challenges in ensuring reliable and reproducible biological assays.

The ms is well written and clear, offering a comprehensive overview of the topic. It is of broad interest to the journal’s readership. Accordingly, I recommend acceptance after the authors address a few minor revisions (see below).

1) Throughout the text, there are minor errors such as missing spaces between words. In addition, the use of square brackets for references should be carefully checked and, if necessary, standardized or revised.

2) The resolution of the figure , specifically that of chemical structures, could be improved

3) Table 1: Here it would be nice to know whether the reported value for cisplatin was included as "reported from the literature" in the original article.

4) Data reported in the tables: I would like to see the proper references also in the tables' caption.

5) Table 5: DMSO likely refers to the vehicle control used in the experiments. Since the tested compounds were dissolved in DMSO, the authors probably included a DMSO-only control at the same concentration (percentage) used to deliver the compounds. This ensures that any observed effects are due to the compounds themselves and not to the DMSO solvent. Please clarify.

6) Section 3.1 and 3.2: fully agree, however, I believe this could be better suitable as 3.2. In fact this is a relevant -general- consideration of the authors. Similarly, 3.2 is better suitable as 3.1. 

Author Response

Please see the attachment.

Author Response File: Author Response.docx