Reem A. Islim, Nisreen S. Hamadeh, Reema Abu Khalaf, Rima Hajjo, Sanaa K. Bardaweel, Kamal Sweidan, Aya M. Al-Zuheiri, Swapnaa Balaji, Amit K. Tiwari, Ghassan Abushaikha, Dima A. Sabbah
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Analogue <b>11</b> showed 100% inhibitory activity against ovarian cancer (NCI/ADR-RES), colon cancer (COLO 205), CNS cancer (SF-295), and melanoma (SK-MEL-2) cells. Cheminformatics analysis further revealed insights into the physicochemical and drug-like properties of these analogues, highlighting their potential to bind PI3Kα through alignment with key pharmacophoric features required for effective enzyme interaction. Molecular docking studies against both wild-type and mutant PI3Kα elucidated binding interactions, suggesting that specific substituents enhance selectivity and potency. This study highlights the therapeutic potential of quinolone derivatives in targeting cancer-related pathways and contributes valuable data to the ongoing search for more effective anticancer therapies.</p></div>","PeriodicalId":496,"journal":{"name":"BMC Chemistry","volume":"19 1","pages":""},"PeriodicalIF":4.3000,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://bmcchem.biomedcentral.com/counter/pdf/10.1186/s13065-025-01616-w","citationCount":"0","resultStr":"{\"title\":\"Exploring the anticancer potential of nitrated N-substituted-4-hydroxy-2-quinolone-3-carboxamides: synthesis, biological assessment, and computational analysis\",\"authors\":\"Reem A. Islim, Nisreen S. Hamadeh, Reema Abu Khalaf, Rima Hajjo, Sanaa K. Bardaweel, Kamal Sweidan, Aya M. Al-Zuheiri, Swapnaa Balaji, Amit K. Tiwari, Ghassan Abushaikha, Dima A. Sabbah\",\"doi\":\"10.1186/s13065-025-01616-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Cancer remains the second leading cause of mortality globally, necessitating the development of novel therapeutic agents. In this work, we synthesized 34 derivatives of nitrated <i>N</i>-substituted-4-hydroxy-2-quinolone-3-carboxamides, which were spectroscopically analyzed using FT-IR, NMR (<sup>1</sup>H and <sup>13</sup>C), and elemental analysis. Derivatives tailored with <i>m</i>-CF<sub>3</sub> (<b>10</b>), <i>m</i>-OCH<sub>3</sub> (<b>13</b>), <i>m</i>-Cl (<b>16</b>), and <i>m</i>-F (<b>20</b>) benzyl moiety exhibited distinctive cytotoxicity against human colon cancer (HCT-116) cells with IC<sub>50s</sub> of 23.41, 27.14, 28.43, and 22.95 µM. Analogue <b>11</b> showed 100% inhibitory activity against ovarian cancer (NCI/ADR-RES), colon cancer (COLO 205), CNS cancer (SF-295), and melanoma (SK-MEL-2) cells. Cheminformatics analysis further revealed insights into the physicochemical and drug-like properties of these analogues, highlighting their potential to bind PI3Kα through alignment with key pharmacophoric features required for effective enzyme interaction. Molecular docking studies against both wild-type and mutant PI3Kα elucidated binding interactions, suggesting that specific substituents enhance selectivity and potency. This study highlights the therapeutic potential of quinolone derivatives in targeting cancer-related pathways and contributes valuable data to the ongoing search for more effective anticancer therapies.</p></div>\",\"PeriodicalId\":496,\"journal\":{\"name\":\"BMC Chemistry\",\"volume\":\"19 1\",\"pages\":\"\"},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2025-08-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://bmcchem.biomedcentral.com/counter/pdf/10.1186/s13065-025-01616-w\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BMC Chemistry\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://link.springer.com/article/10.1186/s13065-025-01616-w\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Chemistry","FirstCategoryId":"92","ListUrlMain":"https://link.springer.com/article/10.1186/s13065-025-01616-w","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Exploring the anticancer potential of nitrated N-substituted-4-hydroxy-2-quinolone-3-carboxamides: synthesis, biological assessment, and computational analysis
Cancer remains the second leading cause of mortality globally, necessitating the development of novel therapeutic agents. In this work, we synthesized 34 derivatives of nitrated N-substituted-4-hydroxy-2-quinolone-3-carboxamides, which were spectroscopically analyzed using FT-IR, NMR (1H and 13C), and elemental analysis. Derivatives tailored with m-CF3 (10), m-OCH3 (13), m-Cl (16), and m-F (20) benzyl moiety exhibited distinctive cytotoxicity against human colon cancer (HCT-116) cells with IC50s of 23.41, 27.14, 28.43, and 22.95 µM. Analogue 11 showed 100% inhibitory activity against ovarian cancer (NCI/ADR-RES), colon cancer (COLO 205), CNS cancer (SF-295), and melanoma (SK-MEL-2) cells. Cheminformatics analysis further revealed insights into the physicochemical and drug-like properties of these analogues, highlighting their potential to bind PI3Kα through alignment with key pharmacophoric features required for effective enzyme interaction. Molecular docking studies against both wild-type and mutant PI3Kα elucidated binding interactions, suggesting that specific substituents enhance selectivity and potency. This study highlights the therapeutic potential of quinolone derivatives in targeting cancer-related pathways and contributes valuable data to the ongoing search for more effective anticancer therapies.
期刊介绍：
BMC Chemistry, formerly known as Chemistry Central Journal, is now part of the BMC series journals family.
Chemistry Central Journal has served the chemistry community as a trusted open access resource for more than 10 years – and we are delighted to announce the next step on its journey. In January 2019 the journal has been renamed BMC Chemistry and now strengthens the BMC series footprint in the physical sciences by publishing quality articles and by pushing the boundaries of open chemistry.
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