Exploring the Anticancer Potential of NO-Donor Oxadiazole Assemblies Against Malignant Pleural Mesothelioma
, Alexander A. Larin 1,†, Egor M. Matnurov 3,†, Ivan V. Ananyev 4, Maria V. Babak 3,* and Leonid L. Fershtat 1,*
Round 1
Reviewer 1 Report
Comments and Suggestions for Authors
The authors, in the paper entitled Exploring the anticancer potential of NO-donor oxadiazole assemblies against malignant pleural mesothelioma', proposed a simple synthetic route for the preparation of (1,2,4-oxadiazolyl)furoxans. The structure of the compounds was confirmed by X-ray diffraction analysis of one of them. The authors, also tested the anticancer properties of synthesized oxadiazolylfuroxans against a murine mesothelioma cell line (AB1) human mesothelioma cell line (JU77) and human embryonic lung fibroblasts (MRC-5), in comparison with cisplatin.
The work has been carried out in a scientific manner and the analysis is in line with the objectives. The synthesis of the new compounds and the attempt to associate anticancer effects with NO release is commendable.
Before publication, the authors must define all acronyms such as TEA, CDI, DBU, DABCO, etc.
Author Response
Comment 1: [The authors, in the paper entitled Exploring the anticancer potential of NO-donor oxadiazole assemblies against malignant pleural mesothelioma', proposed a simple synthetic route for the preparation of (1,2,4-oxadiazolyl)furoxans. The structure of the compounds was confirmed by X-ray diffraction analysis of one of them. The authors, also tested the anticancer properties of synthesized oxadiazolylfuroxans against a murine mesothelioma cell line (AB1) human mesothelioma cell line (JU77) and human embryonic lung fibroblasts (MRC-5), in comparison with cisplatin. The work has been carried out in a scientific manner and the analysis is in line with the objectives. The synthesis of the new compounds and the attempt to associate anticancer effects with NO release is commendable. Before publication, the authors must define all acronyms such as TEA, CDI, DBU, DABCO, etc.]
Response 1: [Dear Reviewer 1, we thank you for the positive evaluation of our work. Following your suggestion, we defined all the acronyms in the text.]
Reviewer 2 Report
Comments and Suggestions for AuthorsAnticancer research attracts ever-increasing attention from academia and pharmaceutical companies. In particular, new compounds against aggressive and resistant cancer lines are of particular importance. The authors report the synthesis of the new series of organic oxadiazoles, capable of releasing and oversaturating cancer cells with the NO triggering their death. Overall, the topic is highly important as it focuses on the treatment of Malignant Pleural Mesothelioma (MPM), which has a very low survival rate of 5% for patients. Synthesis and characterization of the compounds are well-described.
Authors report an interesting correlation that alkyl-substituted compound 2f practically shows no potency as an anti-cancer drug, whereas all other aryl-substituted compounds show a pronounced effect on all cancer cell lines. Could authors comment on this or compare with literature (if possible) and potentially develop the discussion on the molecular design aspect?
The article contains a balanced citation of the relevant works on synthesis and anticancer properties against MPM. They performed a detailed optimization of their protocol to to obtain the desired compounds. This work will be an important addition and contains interesting findings for the community, which will attract additional readership to Pharmaceutics. The article is clearly written and contains sufficient sections on experimental protocols and methods to reproduce and use the results by other researchers. The conclusions are fully based on the observed experimental data and correlations while outlining the future direction of the work. I recommend accepting this work with minor revisions.
Author Response
Comment 1: [Anticancer research attracts ever-increasing attention from academia and pharmaceutical companies. In particular, new compounds against aggressive and resistant cancer lines are of particular importance. The authors report the synthesis of the new series of organic oxadiazoles, capable of releasing and oversaturating cancer cells with the NO triggering their death. Overall, the topic is highly important as it focuses on the treatment of Malignant Pleural Mesothelioma (MPM), which has a very low survival rate of 5% for patients. Synthesis and characterization of the compounds are well-described.]
Response 1: [Dear Reviewer 2, we thank you for the positive evaluation of our work].
Comment 2: [Authors report an interesting correlation that alkyl-substituted compound 2f practically shows no potency as an anti-cancer drug, whereas all other aryl-substituted compounds show a pronounced effect on all cancer cell lines. Could authors comment on this or compare with literature (if possible) and potentially develop the discussion on the molecular design aspect?]
Response 2: [Following your suggestion, we added the following sentence in the discussion: “The reasons for the absence of cytotoxicity in 2f remain unclear. However, it leads to a conclusion that the methoxy substituent at the C(5) carbon atom of the 1,2,4-oxadiazole ring is not a favorable structural element from the molecular design aspect.”]
