Flavone-based dual PARP-Tubulin inhibitor manifesting efficacy against endometrial cancer
Structural tailoring of the flavone framework (position 7) via organopalladium-catalyzed C–C bond formation was attempted in this study. The impact of substituents with varied electronic effects (phenyl ring, position 2 of the benzopyran scaffold) on the antitumor properties was also assessed. Resul...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2023.2276665 |
| _version_ | 1827123364621189120 |
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| author | Sachin Sharma Kavya Chandra Aliva Naik Anamika Sharma Ram Sharma Amandeep Thakur Ajmer Singh Grewal Ashwani K. Dhingra Arnab Banerjee Jing Ping Liou Santosh Kumar Guru Kunal Nepali |
| author_facet | Sachin Sharma Kavya Chandra Aliva Naik Anamika Sharma Ram Sharma Amandeep Thakur Ajmer Singh Grewal Ashwani K. Dhingra Arnab Banerjee Jing Ping Liou Santosh Kumar Guru Kunal Nepali |
| author_sort | Sachin Sharma |
| collection | DOAJ |
| description | Structural tailoring of the flavone framework (position 7) via organopalladium-catalyzed C–C bond formation was attempted in this study. The impact of substituents with varied electronic effects (phenyl ring, position 2 of the benzopyran scaffold) on the antitumor properties was also assessed. Resultantly, the efforts yielded a furyl arm bearing benzopyran possessing a 4-fluoro phenyl ring (position 2) (14) that manifested a magnificent antitumor profile against the Ishikawa cell lines mediated through dual inhibition of PARP and tubulin [(IC50 (PARP1) = 74 nM, IC50 (PARP2) = 109 nM) and tubulin (IC50 = 1.4 µM)]. Further investigations confirmed the ability of 14 to induce apoptosis as well as autophagy and cause cell cycle arrest at the G2/M phase. Overall, the outcome of the study culminated in a tractable dual PARP-tubulin inhibitor endowed with an impressive activity profile against endometrial cancer. |
| first_indexed | 2024-03-09T02:03:07Z |
| format | Article |
| id | doaj.art-b1897a82d93346ca9c92c10cb9b6ff60 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2025-03-20T14:23:45Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-b1897a82d93346ca9c92c10cb9b6ff602024-09-09T17:23:19ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742023-12-0138110.1080/14756366.2023.2276665Flavone-based dual PARP-Tubulin inhibitor manifesting efficacy against endometrial cancerSachin Sharma0Kavya Chandra1Aliva Naik2Anamika Sharma3Ram Sharma4Amandeep Thakur5Ajmer Singh Grewal6Ashwani K. Dhingra7Arnab Banerjee8Jing Ping Liou9Santosh Kumar Guru10Kunal Nepali11School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, TaiwanDepartment of Biological Sciences, BITS Pilani KK Birla Goa campus, Goa, IndiaDepartment of Biological Sciences, National Institute of Pharmaceutical Education and Research, Hyderabad, IndiaDepartment of Biological Sciences, National Institute of Pharmaceutical Education and Research, Hyderabad, IndiaSchool of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, TaiwanSchool of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, TaiwanGuru Gobind Singh College of Pharmacy, Yamuna Nagar, IndiaGuru Gobind Singh College of Pharmacy, Yamuna Nagar, IndiaDepartment of Biological Sciences, BITS Pilani KK Birla Goa campus, Goa, IndiaSchool of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, TaiwanDepartment of Biological Sciences, National Institute of Pharmaceutical Education and Research, Hyderabad, IndiaSchool of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, TaiwanStructural tailoring of the flavone framework (position 7) via organopalladium-catalyzed C–C bond formation was attempted in this study. The impact of substituents with varied electronic effects (phenyl ring, position 2 of the benzopyran scaffold) on the antitumor properties was also assessed. Resultantly, the efforts yielded a furyl arm bearing benzopyran possessing a 4-fluoro phenyl ring (position 2) (14) that manifested a magnificent antitumor profile against the Ishikawa cell lines mediated through dual inhibition of PARP and tubulin [(IC50 (PARP1) = 74 nM, IC50 (PARP2) = 109 nM) and tubulin (IC50 = 1.4 µM)]. Further investigations confirmed the ability of 14 to induce apoptosis as well as autophagy and cause cell cycle arrest at the G2/M phase. Overall, the outcome of the study culminated in a tractable dual PARP-tubulin inhibitor endowed with an impressive activity profile against endometrial cancer.https://www.tandfonline.com/doi/10.1080/14756366.2023.2276665FlavonebenzopyranPARPtubulininhibitorendometrial cancer |
| spellingShingle | Sachin Sharma Kavya Chandra Aliva Naik Anamika Sharma Ram Sharma Amandeep Thakur Ajmer Singh Grewal Ashwani K. Dhingra Arnab Banerjee Jing Ping Liou Santosh Kumar Guru Kunal Nepali Flavone-based dual PARP-Tubulin inhibitor manifesting efficacy against endometrial cancer Journal of Enzyme Inhibition and Medicinal Chemistry Flavone benzopyran PARP tubulin inhibitor endometrial cancer |
| title | Flavone-based dual PARP-Tubulin inhibitor manifesting efficacy against endometrial cancer |
| title_full | Flavone-based dual PARP-Tubulin inhibitor manifesting efficacy against endometrial cancer |
| title_fullStr | Flavone-based dual PARP-Tubulin inhibitor manifesting efficacy against endometrial cancer |
| title_full_unstemmed | Flavone-based dual PARP-Tubulin inhibitor manifesting efficacy against endometrial cancer |
| title_short | Flavone-based dual PARP-Tubulin inhibitor manifesting efficacy against endometrial cancer |
| title_sort | flavone based dual parp tubulin inhibitor manifesting efficacy against endometrial cancer |
| topic | Flavone benzopyran PARP tubulin inhibitor endometrial cancer |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2023.2276665 |
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