New Compounds from Terrestrial Plants: A Perspective View

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Based on criteria 2 and 3 used by authors that exclude aquatic plants but include only new compounds with biological activities,  I suggest a new title:

 “New bioactive  compounds from terrestrial plants: a perspective view”

The aim of this review it is clear and defined. But unfortunately the content of each paragraphs are in disagreement with which reported in  paragraph 2

At lines 93-94 authors affirm that “117 complete articles were compiled to compose the review“, but at paragraph 3 authors discuss about 464 articles. Please explain and clarify this key point of reviews structure’s. Specifically, if there are 117 jobs, how can they refer to 122 families?

There are others several doubts regarding paragraph 3 and 4. The selected genus belong to family not are present in table 1 where instead are reported the family with high relative frequency in literature data. Please explain.

Line 137. Authors affirm that: “One hundred forty-six new compounds were isolated, with most part belonging to the 137 terpene class”, but the number of new compounds reported in table 2 is 153.

Use the same criteria when drawing all structures. E.G. glucose or in Haworth projection or as chain ring or planar structures (30 vs 3 vs 10), delete H Unnecessary (35, 50, 52). Please specify “R” in structure 54

Lines 150-152. As authors introduce the different types of compounds isolated from genus Piper it is better , so rephrase as suggested .

“Polyketides (Kavalactones), alkaloids (atistolactams), polyphenols (lignoids, chromones), simple phenols (phenylpropanoids, prenylated benzoic acids) and terpenes ( monoterpenes, sesquiterpenes) are the main secondary compounds produced by plants of the genus Piper, which give it economic and medicinal importance”

5.1 section

The numeration of structures 1-19 is wrong compared to what is reported in the main text lines 314-357

The correct structure of Hyperiforins A and C are the compounds 1 and 2 , respectively.

line 323. The correct structure of glycosidic monoterpene compound is 3 and not 4 as reported in the main text. Please draw the OH linked to C-3 in equatorial position.

rephrase the sentence “Three new glycosidic monoterpene compounds (4) (with glucopyranosyl and apio- furanosyl groups) derived from Carvacrol were obtained from the roots of Lilium dauricum Ker Gawl. (Liliaceae). It is interesting to note that, despite the small structural difference 325 (exchange of the position of the sugars and methyl), different potency in the α-glucosidase inhibitory action was found (48)”  as authors report only one compound.  However in the reference 48 (Planta Med., 2022, 88 (7), 518–526. ) really Three new glycosidic have been isolated. Please check the mistake.

other remarks:

line 184 change Bacillus subtilis with B. subtilis

Lines 222-223 and Lines 296-297  not uppercase.

line 225 change “Two new compounds derived from thiophene and a new sesquiterpene“ with “new thiophene derivatives and a new sesquiterpene”

errors of typos:

line 63 tittles

lines 108-110 delete % after 18, 16 and 16 respectively, as this numbers represents absolute frequency

line 150 change Cavalactones with the right name Kavalactones

Author Response

Reviewer: 1

Based on criteria 2 and 3 used by authors that exclude aquatic plants but include only new compounds with biological activities, I suggest a new title:

 “New bioactive compounds from terrestrial plants: a perspective view”

- We have added the term "terrestrial" as suggested by the reviewer. The term “bioactive” was not included, as studies did not always report activity for new isolated compounds.

The aim of this review it is clear and defined. But unfortunately the content of each paragraphs are in disagreement with which reported in  paragraph 2

At lines 93-94 authors affirm that “117 complete articles were compiled to compose the review“, but at paragraph 3 authors discuss about 464 articles. Please explain and clarify this key point of reviews structure’s. Specifically, if there are 117 jobs, how can they refer to 122 families?

- We identified 464 studies that met our eligibility criteria. From these articles, we gathered methodological information including the botanical family, genus, and species studied, the class of compound elucidated, the plant organ where the compound was found, and the journal in which the study was published.

Due to the large number of articles, we selected 117 studies out of the 464 to discussion in this paper.

We recognize that the methodology was confusingly described, so we have modified it for better understanding.

There are others several doubts regarding paragraph 3 and 4. The selected genus belong to family not are present in table 1 where instead are reported the family with high relative frequency in literature data. Please explain.

- In the discussed sections, we highlight selected genera that, indeed, do not appear in Table 1. This table showcases families with the highest relative frequency of mention in the literature, not necessarily the genera. It's essential to understand that the most frequently occurring genera may not belong to the most frequently mentioned families due to the presence of other genera within these families. This discrepancy was an intentional choice to underscore the significance of certain genera that, despite their less frequent appearance in literature as part of broader families, have contributed novel chemical structures of interest.

Line 137. Authors affirm that: “One hundred forty-six new compounds were isolated, with most part belonging to the 137 terpene class”, but the number of new compounds reported in table 2 is 153.

- Thank you for the observation. We made a mistake in this sentence; the correct number is 153.

Use the same criteria when drawing all structures. E.G. glucose or in Haworth projection or as chain ring or planar structures (30 vs 3 vs 10), delete H Unnecessary (35, 50, 52). Please specify “R” in structure 54.

• Modifications were made as suggested by the reviewer.

Lines 150-152. As authors introduce the different types of compounds isolated from genus Piper it is better , so rephrase as suggested .

“Polyketides (Kavalactones), alkaloids (atistolactams), polyphenols (lignoids, chromones), simple phenols (phenylpropanoids , prenylated benzoic acids) and  terpenes ( monoterpenes, sesquiterpenes) are the main secondary compounds produced by plants of the genus Piper, which give it economic and medicinal importance”

• Modifications were made as suggested by the reviewer.

5.1 section

The numeration of structures 1-19 is wrong compared to what is reported in the main text lines 314-357

The correct structure of Hyperiforins A and C are the compounds 1 and 2 , respectively.

• We reviewed the numbering of all structures.

line 323 The correct structure of glycosidic monoterpene compound is 3 and not 4 as reported in the main text. Please draw the OH linked to C-3 in equatorial position.

• The comment is no longer applicable as sugars are no longer drawn in the Haworth projection.

rephrase the sentence “Three new glycosidic monoterpene compounds (4) (with glucopyranosyl and apio- furanosyl groups) derived from Carvacrol were obtained from the roots of Lilium dauricum Ker Gawl. (Liliaceae). It is interesting to note that, despite the small structural difference 325 (exchange of the position of the sugars and methyl), different potency in the α-glucosidase inhibitory action was found (48)”  as authors report only one compound.  However in the reference 48 (Planta Med., 2022, 88 (7), 518–526. ) really Three new glycosidic have been isolated. Please check the mistake.

• We double-checked the reference, and changed the text to: “New glycosidic monoterpene compounds…”

other remarks:

line 184 change Bacillus subtilis with B. subtilis

Lines 222-223 and Lines 296-297  not uppercase.

line 225 change “ Two new compounds derived from thiophene and a new sesquiterpene “ with “new thiophene derivatives and a new sesquiterpene”

errors of typos:

line 63 tittles

lines 108-110 delete % after 18, 16 and 16 respectively, as this numbers represents absolute frequency

line 150 change Cavalactones with the right name Kavalactones

• Modifications were made as suggested by the reviewer.

Reviewer 2 Report

Comments and Suggestions for Authors

This is an interesting review on the reports dealing with isolation of new plant derived compounds. The most investigated plant families were identified, as well the main classes of compounds. However, the data bases survey comprises only 2021-2022, but today is 2024. So, in my opinion this analysis should also take into consideration at least a half of 2023 year.

There are some more aspects that require improvements.

Specific remarks:

1)     Abstract: why it starts from: “In view of the diminishing contribution of natural products from plants to the discovery of new chemical structures..” -?

2)     Reference style should be adjust to the Journal requirements.

3)     What plant parts have been used for isolation of new compounds? In many cases there is lack of such information.

4)     There is no need to write the name of compound using Capital letter in the middle of the sentence.

5)     Typing errors should be removed.

6)     English grammar errors should be corrected.

7)     Latin names of plant species and genera should be written using Italic font.

8)     Lines: 295-296 – unclear; and Figure 1 instead of Graph 1. Further, Graph 1 legend should be improved, in present form is unclear;

9)     There is no Figure number and legend for presented structures of compounds, the enumeration of them in the text is not enough;

10)  Line 384, 464: one author’s studies?

Comments on the Quality of English Language

English grammar errors should be corrected.

Author Response

Reviewer: 2

This is an interesting review on the reports dealing with isolation of new plant derived compounds. The most investigated plant families were identified, as well the main classes of compounds. However, the data bases survey comprises only 2021-2022, but today is 2024. So, in my opinion this analysis should also take into consideration at least a half of 2023 year.

-Thank you for your feedback. We recognize the importance of including more recent data up to 2023 in our analysis. However, the extensive scope of our review, encompassing a vast array of articles published in 2021 and 2022, necessitated a considerable amount of time for thorough data analysis and writing. Our aim was to provide a detailed snapshot of the main molecules, plant families, and genera studied during this period, offering valuable insights into the trends and directions of plant-derived compound research at that time. We believe this temporal focus allows for a comprehensive understanding of the field's progression during these years.

There are some more aspects that require improvements.

Specific remarks:

1)     Abstract: why it starts from: “In view of the diminishing contribution of natural products from plants to the discovery of new chemical structures..” -?

We appreciate the comment and have changed it to: “In an era where the search for innovative drug leads faces challenges, our study pivots towards exploring the untapped potential of plant-derived compounds, focusing on the period of 2021 to 2022, assessing: …”

2)     Reference style should be adjust to the Journal requirements.

- Modifications were made as suggested by the reviewer.

3)     What plant parts have been used for isolation of new compounds? In many cases there is lack of such information.

- We acknowledge your concern, however, It's important to note that our review focuses primarily on identifying and cataloging new chemical structures derived from plants, their classes, and the plant families to which they belong, rather than detailing the specific plant parts used in these studies. This scope was chosen to streamline our analysis and highlight the most impactful findings in the field within our review period. We believe that specifying plant parts, while valuable, falls outside the central aims of our current study.

4)     There is no need to write the name of compound using Capital letter in the middle of the sentence.

- Modifications were made as suggested by the reviewer.

5)     Typing errors should be removed.

6)     English grammar errors should be corrected.

7)     Latin names of plant species and genera should be written using Italic font.

Coments to 5-7: Thank you for the feedback. We have addressed the typing and grammar errors and ensure that all Latin names of plant species and genera are correctly italicized.

8)     Lines: 295-296 – unclear; and Figure 1 instead of Graph 1. Further, Graph 1 legend should be improved, in present form is unclear;

- Modifications were made as suggested by the reviewer.

9)     There is no Figure number and legend for presented structures of compounds, the enumeration of them in the text is not enough;

- Thank you for your observation regarding the presentation of compound structures without figure numbers and legends. However, the format adopted in our manuscript aligns with the editorial style commonly utilized by journals in our field and it is consistent with precedents set by previous publications in this journal.

10)  Line 384, 464: one author’s studies?

- Modifications were made. There are several authors.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The comments are reported in attached file

Comments for author File: Comments.pdf

Author Response

We would like to extend our sincere gratitude for your insightful suggestions and the valuable corrections you provided for our manuscript. We want to inform you that we have thoroughly implemented all the suggested corrections and meticulously reviewed all the chemical structures in accordance with your recommendations. Additionally, we have revisited the previous suggestions you provided and have ensured that each one has been fully addressed and integrated into the revised manuscript.

We believe these revisions have significantly improved the quality and clarity of our work. We are looking forward to your feedback and are hopeful that our manuscript now is suitable for publication.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors I recommend this manuscript for publication.

Author Response

Thank you