{"title":"Anti-Cancer Activity Evaluation of Naphthalenonic and Chromanonic\u0000Spiroisoxazoline Derivatives as Selective COX-2 Inhibitors on HT29 Cell\u0000Lines","authors":"Hourieh Kalhor, Tahereh Komeili Movahhed, S. Mousavi, Masoumeh Sadri Qomi, A. Abolhasani, Masoumeh Mirani, Minoo Hosseini Rad, Fatemeh Heidari, Hoda Hosseini","doi":"10.2174/012212697x274833240408033609","DOIUrl":"https://doi.org/10.2174/012212697x274833240408033609","url":null,"abstract":"\u0000\u0000Cyclooxygenase-2 (COX-2) is induced in response to proinflammatory\u0000conditions, and it is not only a key enzyme in the inflammatory process, but also seems to be\u0000highly expressed in various types of cancer cells. On the other hand, it is well documented that\u0000chemical compounds with spiro scaffolds in their structure could be effective chemical agents\u0000against cancer types.\u0000\u0000\u0000\u0000In this study, the cytotoxicity effects of spiroisoxazoline derivatives containing naphthalinone and chromanone spiro-bridge were investigated.\u0000\u0000\u0000\u0000The cytotoxicity effects of compounds 7a-7h were evaluated by performing the MTT\u0000assay on the HT-29 (colorectal cancer), MCF-7 (breast cancer), and HEK-293 (normal kidney)\u0000cell lines. After that, a compound with high yield and remarkable cytotoxic activity was selected\u0000to analyze the cell cycle and apoptosis mechanism.\u0000\u0000\u0000\u0000The most effective cytotoxic activity was observed on HT-29 and MCF-7 cell lines of\u0000compounds 7b (IC50 value: 1.07±0.28 µM) and 7f (IC50 value: 11.92±1.07 µM). None of the\u0000compounds had a toxic effect on normal HEK-293 cells, except for compound 7g with an IC50\u0000value of 21.30±16.14 µM, whose effect was much lower than that of cisplatin and doxorubicin,\u0000known as anti-cancer agents. Subsequently, compound 7e with significant yield and cytotoxic\u0000activity was investigated to evaluate cell cycle and apoptosis. The result showed that compound\u00007e induced significant G0/G1 cell cycle arrest and apoptosis in HT-29 cells\u0000\u0000\u0000\u0000The selective COX-2 inhibitor compounds with spiroisoxazoline core structure\u0000could be suitable scaffolds for cytotoxic effects.\u0000","PeriodicalId":91228,"journal":{"name":"Clinical cancer drugs","volume":"131 46","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141656302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}