Review Reports

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The paper adequately describes the current state of research in the field of repurposing antimalarials for the treatment of cancer. The review contains appropriate references and is incredibly thorough.  There a few minor suggestions noted below that would improve the readability.

 

Figure 2 - Consider rephrasing "Emerge Metabolism" to simple metabolism or alterations in metabolism.

Table 1 - While incredibly thorough, it seems too long for the main manuscript. Perhaps highlight or group similar drugs, find another way to condense, or move portions to a supplemental section.

Each section contains all the required information, but is written more as a list then a comprehensive review. Perhaps adding a summary to each section to highlight key data or adding transitions between related topics would improve the flow of the paper.

 

Author Response

Comments1: [The paper adequately describes the current state of research in the field of repurposing antimalarials for the treatment of cancer. The review contains appropriate references and is incredibly thorough. There a few minor suggestions noted below that would improve the readability.

Figure 2 - Consider rephrasing "Emerge Metabolism" to simple metabolism or alterations in metabolism.]

Response: Thank you very much for the careful and detailed review. We have revised “Emerge Metabolism” to “Metabolism” in Figure 2 (Page 3) to improve clarity and accuracy.

 

Comments2: [Table 1 - While incredibly thorough, it seems too long for the main manuscript. Perhaps highlight or group similar drugs, find another way to condense, or move portions to a supplemental section.]

Response: Thank you very much for the careful and detailed review. To balance completeness with readability, we have moved the original Table 1 to the Supplementary Materials (now Supplementary Table S1). This change has significantly improved the flow of the main text.

 

Comments3: [Each section contains all the required information, but is written more as a list then a comprehensive review. Perhaps adding a summary to each section to highlight key data or adding transitions between related topics would improve the flow of the paper.]

Response: Thank you very much for the careful and detailed review. We have revised all major sections by adding a short summary paragraph at the end of each section to highlight key findings. These revisions have improved the overall flow, making the manuscript read more like a cohesive review.

Reviewer 2 Report

Comments and Suggestions for Authors The authors have summarized the anticancer potential of dihydroartemisinin in this review. They cover all biological details, e.g. mechanism, apoptosis, autophagy, immune and migration studies, and even present clinical trials, etc. The tables contain all important data (Table 3.: in"vitor" must be correct), the structures of known derivatives are also presented. Although this publication can be considered an important and excellent work, one supplement should be added. It can be seen  in the dihydroartemisinin derivatives in question that the pharmacophor molecules are coupled always in the same position, so thus, a typical reaction scheme for their preparation should be presented. It is definitely recommened adding this.

Author Response

Comments1: [The authors have summarized the anticancer potential of dihydroartemisinin in this review. They cover all biological details, e.g. mechanism, apoptosis, autophagy, immune and migration studies, and even present clinical trials, etc. The tables contain all important data (Table 3.: in"vitor" must be correct), the structures of known derivatives are also presented.]

Response: Thank you very much for the careful and detailed review. We have corrected the type in Table 3 (Page 23), changing “in vitor” to the correct “in vitro”. We have also proofread the entire manuscript again to ensure no similar errors remain.

 

Comments2: [Although this publication can be considered an important and excellent work, one supplement should be added. It can be seen in the dihydroartemisinin derivatives in question that the pharmacophore molecules are coupled always in the same position, so thus, a typical reaction scheme for their preparation should be presented. It is definitely recommended adding this.]

Response: Thank you very much for the careful and detailed review. In response, we have added a typical reaction scheme for the preparation of dihydroartemisinin derivatives in the corresponding section of the manuscript.(Page 13) The accompanying description now reads as follows:

[Notably, in the structure of DHA, only the hydroxyl group is a relatively reactive modification site, while other sites exhibit low reactivity without disrupting the original structure. Therefore, in traditional methods, modifications are exclusively targeted at this site, typically by forming an ether bond with the hydroxyl group at the C10 position of DHA under the catalysis of BF3·OEt2, thereby introducing the hybrid group.]