Synthesis, Antimicrobial and Antiproliferative Activity of 1-Trifluoromethylphenyl-3-(4-arylthiazol-2-yl)thioureas

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The manuscript reports the synthesis of a library different positional CF₃ substituted thiazolyl-thiourea derivatives and in vitro evaluation for antimicrobial, antimycobacterial, and antiproliferative activities. The work addresses an important medicinal chemistry problem identification of new scaffolds to combat antimicrobial resistance and cancer and combines sound synthetic chemistry with broad biological screening. Overall, the study is technically solid, and of moderate novelty, with several compounds showing promising antimicrobial profiles. The manuscript is suitable for publication after addressing below minor comments.

Comments,

1. The manuscript requires substantial language editing. Please see few highlighted sections contain unclear or poorly constructed sentences that need to be revised for clarity and readability in abstract section, but it is recommended to revise the whole manuscript for better readability.
2. The MIC values (µg mL⁻¹) reported for compounds 7i and 11h in Table 1 appear to be the same. The authors are requested to recheck and confirm the accuracy of these data.

• No selectivity or cytotoxicity data toward normal mammalian cells are provided, which limits interpretation of therapeutic potential. It is recommended to include such data if any.

1. The manuscript would benefit from a brief discussion on why CF₃ groups were emphasized beyond lipophilicity.
2. Adding a short mechanistic rational for the observed activities different analogues would enhance the discussion section.
3. The identification of 7i and 11h as potent antifungal/antibacterial leads, and 9g/11g as antimycobacterial hits adds incremental but meaningful value. It would be interesting if authors discuss and highlight how these compounds improve upon or differ from previously reported thiazolyl-thioureas in terms of potency, selectivity, or spectrum etc,.

 

Comments for author File: Comments.pdf

Author Response

"Please see the attachment".

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The manuscript with title "Synthesis, antimicrobial and antiproliferative activity of 1-tri- fluoromethylphenyl-3-(4-arylthiazol-2-yl)thioureas" is presented a synthesis of 24 new 1-aryl-3-(4-arylthiazol-2-yl)thioureas derivatives. The literature cited in this paper is sufficient in volume and content (references are 43). The all 3 Tables are with sufficiently high quality. This paper should be of particular interest to the readers of your journal because many researchers have paid attention to the antimicrobial and antiproliferative activity of different biological active compounds.

In addition, the authors should address the following points carefully to improve the quality of manuscript.

Dear Authors!

Please revisit the article with reg. no. 4075373 in accordance with Editor’s comments:

Major point:

1. Line 12: A549, HeLa, IMR32, MCF-7, HCT116 and DU145 human cancer cell lines. Give abbreviation of these six tumor cell line. (A549 (human lung adenocarcinoma epithelial cells), HeLa (human cervical carcinoma cells), IMR32 (human neuroblastoma cells), MCF-7 (human breast adenocarcinoma cells), HCT116 (human colon cancer cells) and DU145 (human prostate cancer cells)).
2. Line 58: Why the structure of 2,3-dihydro-6-propyl-2-thioxopyrimidin-4(1H)-one (4) are shown in Figure 1? In scheme 1 6-propyl-2-thiouracil didn’t have participation.
3. Line 154: Point 3. Results and Discussion, 3.1. Chemistry. After Scheme 1, you can include the IR, ¹H, ¹³C and EI-MS, HRMS results of the compounds from supplementary materials.
4. Table S1 Molecular and physical characteristics of target compounds (7a-i, 9a-g and 11a-h), pg.8 from supplementary materials: How would you explain the lower yield of substances 9a-9g and 11a-11h? (73-71%)
5. Line 186: Table 1. In vitro antibacterial and antifungal activities of the thioureas and standards (MIC μg mL⁻¹)^a. The antibacterial and antifungal activities of the compounds 7a, 7b, 7c,7d and 9b, 9c, 9d, 9h, as well as 11a, 11c, 11d, 11f are missed.
6. How would you explain the lower antibacterial, antifungal and antimycobacterial activities of substances 7a-7d, 9a-9d and 11a-11f?
7. Line 230: “All the twenty four newly synthesized thioureas derivatives were assayed for their anticancer potential against six cell lines comprising of A549 (human lung adenocarcinoma epithelial cells), HeLa (human cervical carcinoma cells), IMR32 (human neuroblastoma cells), MCF-7 (human breast adenocarcinoma cells), HCT116 (human colon cancer cells) and DU145 (human prostate cancer cells), using doxorubicin and combretastatin as standard drugs for comparison.” Provide quantitative data on cytotoxic activity in section 4. Conclusions

 

Minor points:

1. Line 130 “CO2” must be CO₂.
2. 10 in supplementary materials: compound 10c must be 11c (Table S1 Molecular and physical characteristics of target compounds (7a-i, 9a-g and 11a-h)).

 

I recommend that the journal editors accept the article with minor grammatical and technically corrections.

 

 

 

Comments for author File: Comments.pdf

Author Response

"Please see the attachment."

Author Response File: Author Response.pdf