Exploring the Anticancer Potential of NO-Donor Oxadiazole Assemblies Against Malignant Pleural Mesothelioma

Exploring the Anticancer Potential of NO-Donor Oxadiazole Assemblies Against Malignant Pleural Mesothelioma Full article

Journal

Pharmaceutics
ISSN: 1999-4923

Output data

Year: 2025, Volume: 17, Number: 2, Article number : 230, Pages count : DOI: 10.3390/pharmaceutics17020230

Authors

Stebletsova Irina A. ^1,2 , Larin Alexander A. ² , Matnurov Egor M. ³ , Ananyev Ivan V. ⁴ , Babak Maria V. ³ , Fershtat Leonid L. ²

Affiliations

1	Higher Chemical College of the Russian Academy of Science, D.I. Mendeleev University of Chemical Technology of Russia, 9 Miusskaya Square, 125047 Moscow, Russia
2	N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky Prosp., 119991 Moscow, Russia
3	Drug Discovery Lab, Department of Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Hong Kong SAR 999077, China
4	N.S. Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences, 31 Leninsky Prosp., 119991 Moscow, Russia

Background: Nitric oxide (NO) has been linked to the pathogenesis of asbestos-related pleural diseases, including an extremely aggressive cancer called malignant pleural mesothelioma (MPM). Given that MPM cells are characterized by a higher expression of NO synthases and elevated NO production relative to normal cells, the use of NO-donor compounds could potentially saturate the cancerous cells with NO, triggering their death. Methods: We developed a novel class of NO prodrugs by merging two NO-releasing components, 1,2,5-oxadiazole 2-oxides (furoxans) and 1,2,4-oxadiazoles, and studied their NO-releasing characteristics in a time-dependent manner using the Griess assay. The cytotoxicity against two human MPM cell lines and non-cancerous lung fibroblasts was evaluated using a colorimetric MTT assay. Results: All compounds exhibited excellent NO-donating properties, surpassing the capacity of two reference NO donor compounds, 3-carbamoyl-4-(hydroxymethyl)furoxan (CAS-1609) and 4-ethoxy-3-phenylsulphonylfuroxan (CHF-2363), by at least 1.5–3 times. All oxadiazole hybrids demonstrated high cytotoxicity against MPM cell lines in a low micromolar range, comparable or higher than the cytotoxicity of the standard-of-care drug cisplatin. Conclusions: Notably, the novel compounds displayed a markedly greater selectivity towards cancerous cells than cisplatin when compared with non-cancerous lung fibroblasts, aligning with the intended design.

Stebletsova I.A. , Larin A.A. , Matnurov E.M. , Ananyev I.V. , Babak M.V. , Fershtat L.L.
Exploring the Anticancer Potential of NO-Donor Oxadiazole Assemblies Against Malignant Pleural Mesothelioma
Pharmaceutics. 2025. V.17. N2. 230 . DOI: 10.3390/pharmaceutics17020230 WOS OpenAlex

Web of science:	WOS:001429639300001
OpenAlex:	W4407351525

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