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MPM cells show higher expression of NO synthases and elevated NO production, motivating NO-donor prodrugs to overload cancer cells with NO and trigger death. A new NO-donor class was synthesized by combining furoxans and 1,2,4-oxadiazoles, with NO release characterized by time-dependent Griess assays. Cytotoxicity was tested on MPM cell lines and non-cancer lung fibroblasts via MTT assay.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/exploring-the-anticancer-potential-of-no-donor-oxadiazole-assemblies-against-malignant-pleural-mesothelioma/372161/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/exploring-the-anticancer-potential-of-no-donor-oxadiazole-assemblies-against-malignant-pleural-mesothelioma/372161.png","ImageObject",300,407,{"name":92,"@type":93},"Noah","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-28","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why are NO-donor compounds considered for malignant pleural mesothelioma (MPM)?","Question",{"text":112,"@type":113},"MPM cells often express higher levels of NO synthases and produce more NO than normal cells. The study rationale is that NO-donor prodrugs could saturate cancerous cells with NO and induce death.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were the NO-donating properties of the synthesized compounds evaluated?",{"text":117,"@type":113},"NO release was assessed in a time-dependent manner using the Griess assay after developing the novel NO prodrugs by combining furoxans and 1,2,4-oxadiazoles.",{"name":119,"@type":110,"acceptedAnswer":120},"What did the study find regarding cytotoxicity and comparison with standard treatment?",{"text":121,"@type":113},"The compounds showed high cytotoxicity against MPM cell lines in the low micromolar range, comparable to or higher than cisplatin. They also demonstrated greater selectivity toward cancerous cells than cisplatin when compared with non-cancerous lung fibroblasts.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},372161,1790463437,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":36},8796095462418,"https://ap-avatar.wpscdn.com/avatar/80000253c1241d02b47?x-image-process=image/resize,m_fixed,w_180,h_180&k=1778826106357471780","Article  \nExploring the Anticancer Potential of NO-Donor Oxadiazole Assemblies Against Malignant Pleural Mesothelioma  \nIrina A. Stebletsova 1,2, Alexander A. Larin 1,†, Egor M. Matnurov 3,†, Ivan V. Ananyev 4, Maria V. Babak 3, * and Leonid L. Fershtat 1, *  \nAcademic Editor: Xiaoyong Wang  \nReceived: 27 December 2024  \nRevised: 31 January 2025  \nAccepted: 4 February 2025  \nPublished: 10 February 2025  \nCitation: 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, 17, 230 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)pharmaceutics17020230  \nCopyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) .  \n1 N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky Prosp.,  \n119991 Moscow, Russia; [irinastebl@icloud.com](irinastebl@icloud.com) (I.A.S.); [roby3@mail.ru](roby3@mail.ru) (A.A.L.)  \n2 Higher Chemical College of the Russian Academy of Science, D.I. Mendeleev University of Chemical Technology of Russia, 9 Miusskaya Square, 125047 Moscow, Russia  \n3 Drug Discovery Lab, Department of Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Hong Kong SAR 999077, China; [ematnurov2-c@my.cityu.edu.hk](ematnurov2-c@my.cityu.edu.hk)  \n4 N.S. Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences, 31 Leninsky  \nProsp., 119991 Moscow, Russia; [ananyev@ineos.ac.ru](ananyev@ineos.ac.ru)  \n* [Correspondence: mbabak@cityu.edu.hk](Correspondence: mbabak@cityu.edu.hk) (M.V.B.); [fershtat@bk.ru](fershtat@bk.ru) (L.L.F.)† These authors contributed equally to this work.  \nAbstract: Background: Nitric oxide (NO) has been linked to the pathogenesis of asbestosrelated 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.  \nKeywords: nitrogen heterocycles; furoxan; oxadiazole; malignant pleural mesothelioma; NO donors; antiproliferative activity  \n1. Introduction  \nMalignant pleural mesothelioma (MPM) is a rare and aggressive cancer that primarily affects the lining of the lungs, called pleura [1]. This malignancy is notorious for its poor prognosis and rapid progression, often leading to devastating outcomes for patients [2]. The primary cause of MPM is the inhalation of asbestos fibers, which can trigger chronic inf","cbCaiko6Ptht3aYw","https://ap.wps.com/l/cbCaiko6Ptht3aYw","pdf",2762380,16,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions\n# Introduction\n## Malignant pleural mesothelioma and current outlook\n## NO in the pleural cavity\n## Rationale for NO-donor anticancer strategy\n## Furoxans and oxadiazole NO prodrugs","[{\"question\":\"Why are NO-donor compounds considered for malignant pleural mesothelioma (MPM)?\",\"answer\":\"MPM cells often express higher levels of NO synthases and produce more NO than normal cells. The study rationale is that NO-donor prodrugs could saturate cancerous cells with NO and induce death.\"},{\"question\":\"How were the NO-donating properties of the synthesized compounds evaluated?\",\"answer\":\"NO release was assessed in a time-dependent manner using the Griess assay after developing the novel NO prodrugs by combining furoxans and 1,2,4-oxadiazoles.\"},{\"question\":\"What did the study find regarding cytotoxicity and comparison with standard treatment?\",\"answer\":\"The compounds showed high cytotoxicity against MPM cell lines in the low micromolar range, comparable to or higher than cisplatin. They also demonstrated greater selectivity toward cancerous cells than cisplatin when compared with non-cancerous lung fibroblasts.\"}]","Exploring the Anticancer Potential of NO-Donor Oxadiazole Assemblies Against Malignant Pleural Mesothelioma | PDF",1790193850]