4-[Bis(thiazol-2-ylamino)methyl]phenol
Round 1
Reviewer 1 Report
I read the work. The work concerns the synthesis of one compound of a thiazole derivative with potential biological activity. The work is based on the known and published method of bis-thiazole synthesis.
Below are some considerations that must be taken into account for the work to meet the requirements and be accepted.
Abstract Line 10 is „Bis-thazole” should be bis-thiazol
Introduction line 25 “However, these inhibitors have numerous side effects such as der- 25 matitis, skin irritation, DNA damage and cancer”. Repharse the sentence inhibitors don’t have any cancer probably they cause/induce cancer
Are the authors sure of their procedure, how is it possible that with an equimolar amount of substrates, where there are two moles of amine for one mole of aldehyde, the product was obtained with 71% yield? Was there an excess of amine?
The chemical purity of the compound should be confirmed by elemental analysis. Other methods, including hplc, are not a confirmation as they depend on the solubility of the compound and impurities.
Some impurities can be seen in the accompanying NMR spectra.
In the absence of confirmation of purity, it is difficult to draw correct conclusions as biological activity may be related to impurity
In addition, it would be worth conducting a statistical analysis to determine the error for the determined values ​​of inhibition activity.
The work after introducing modifications may be considered sufficient for publication
Author Response
I read the work. The work concerns the synthesis of one compound of a thiazole derivative with potential biological activity. The work is based on the known and published method of bis-thiazole synthesis.
Below are some considerations that must be taken into account for the work to meet the requirements and be accepted.
Abstract Line 10 is „Bis-thazole” should be bis-thiazol
Misprint have been corrected.
Introduction line 25 “However, these inhibitors have numerous side effects such as der- 25 matitis, skin irritation, DNA damage and cancer”. Repharse the sentence inhibitors don’t have any cancer probably they cause/induce cancer
The sentence has been rephrased.
Are the authors sure of their procedure, how is it possible that with an equimolar amount of substrates, where there are two moles of amine for one mole of aldehyde, the product was obtained with 71% yield? Was there an excess of amine?
Thank you. Of course we used one mol of aldehyde and two moles of thiazole. We made a few experiments with different molar ratios, and by mistake we have written inappropriate amount of aldehyde. It was corrected to proper amounts in the manuscript.
In the case of an excess of amine, we got more by-products, which made it difficult to isolate the pure product, not only by crystallization but also by flash chromatography.
The chemical purity of the compound should be confirmed by elemental analysis. Other methods, including hplc, are not a confirmation as they depend on the solubility of the compound and impurities. Some impurities can be seen in the accompanying NMR spectra.
During the HPLC analysis, the entire sample was completely dissolved, which means that it does not contain insoluble impurities. Today, HPLC is more commonly used method to determine the purity of drugs than the old elemental analysis method. It allows you to detect impurities even in ppm amounts. HPLC analysis showed a purity of >99%. We have included an integrated chromatogram in supporting information. In our opinion some impurities in the NMR spectra may come from the solvent and they are less than 1%.
In the absence of confirmation of purity, it is difficult to draw correct conclusions as biological activity may be related to impurity.
In addition, it would be worth conducting a statistical analysis to determine the error for the determined values of inhibition activity.
Unfortunately, we cannot agree with this statement. The purity of the compound is more than 99% determined by HPLC. According to USP <891> and Ph. Eur. (2.2.34) substances should have a purity of more than 98.5% (USP <891>) or 98% (Ph. Eur. 2.2.34).
Following your suggestion, we calculated the error for the determined values of inhibition activity. The error for the determined values of inhibition activity is about 1 percent (1.07%; 1.02% and 1,01%) and since we determined the inhibition three times we decided to give the standard deviation.
The work after introducing modifications may be considered sufficient for publication
We do hope that our answers are sufficient and you will find the resubmitted manuscript suitable for publication in Molbank.
Reviewer 2 Report
In this paper, the authors reported the preparation and tyrosinase inhibitory activity of bis-thiazole derivative. Since the manuscript is well written, the reviewer recommend the publication in current form.
Author Response
Thank you.
Round 2
Reviewer 1 Report
The authors made the necessary corrections. The work deserves publication.
Author Response
Thank you for all the suggested comments.
