Methyl 9-(2-Iminothiazol-3(2H)-yl)-9-oxononanoate

Round 1

Reviewer 1 Report

The reviewer comment is attached.

Comments for author File: Comments.pdf

Author Response

Reviewer Comments

We thank the reviewer for the suggestions, and we modified the manuscript, accordingly.

Comments and Suggestions for Authors

The manuscript describes synthesis of methyl 9-(2-iminothiazol-3(2H)-yl)-9-oxononanoate and its biological evaluation. Authors demonstrated preparation of the title compound by Schotten-Baumann type reaction and verification of its chemical structure, which exhibited inhibitory activity on U2OS. I think this manuscript is well-written and appropriate for publication in Molbank, however, a minor revision is needed.

• In line 23, correct “deacetilase” into ‘’deacetylase’’. In line 23 and 26, which is correct

“HDACi” or ‘’HDACI’’.

Answer:

We thank the referee and corrected.

• In Scheme 1, the compound 3 was obtained in 43% yield, however, it was unclear whether its regioisomer was formed (ratio) or It is better to mention this result. In Scheme 2, compound number should be added.

      Answer:

We added a sentence about the absence of the other regioisomer, and inserted compound numbers in Scheme 2.

• The reviewer recommends that NOE correlation of the compound 3 is depicted in Figure, which will be helpful for readers to understand

Answer:

We added arrows in Scheme 2, indicating NOE information (i.e.: irradiation of the signal and recording of positive or no NOE effect)

• Authors found compound 3 had a cell-specific activity. The reviewer would like to understand its comparison to activities of original compounds 9-HSA and SAHA, if it is

Answer:

We thank the reviewer and we added a paragraph, with related references, as follows:

HT-29 cells have a mutation in the p53 gene at position 273, while U2OS are wt for this protein. This difference is important as it explains the different biological responses to therapeutic agents. Indeed, it has been demonstrated that the administration of 9-HSA to HT29 inhibits HDAC1 inducing histone hyperacetylation which is associated to a cytostatic effect [11]. On the contrary, treatment of U2OS produces a hyperacetylation of p53 with consequent cytotoxic effect [16]. Moreover, 9-HSA is a selective inhibitor of class I HDACs [12], while other agents, in particular SAHA (non-selective for HDACi) affects hyperacetylation of all histones and causes massive cell death [17].

Author Response File: Author Response.pdf