دورية أكاديمية
Design, synthesis, and anticancer activity of three novel palbociclib derivatives.
| العنوان: | Design, synthesis, and anticancer activity of three novel palbociclib derivatives. |
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| المؤلفون: | Li T; Department of Cardio-Thoracic Surgery, State Key Laboratory of Pharmaceutical Biotechnology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, School of Life Sciences, Nanjing University, Nanjing, China., Zhou AD; Department of Cardio-Thoracic Surgery, State Key Laboratory of Pharmaceutical Biotechnology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, School of Life Sciences, Nanjing University, Nanjing, China., Bai LF; Jiangsu Key Laboratory of Biofunction Molecule, School of Life Science and Chemical Engineering, Jiangsu Second Normal University, Nanjing, China., Zhang XY; Central Laboratory, Nanjing Integrated Traditional Chinese and Western Medicine Hospital Affiliated with Nanjing University of Chinese Medicine, Nanjing, China., Zhou YT; Department of Cardio-Thoracic Surgery, State Key Laboratory of Pharmaceutical Biotechnology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, School of Life Sciences, Nanjing University, Nanjing, China., Yang HL; Department of Cardio-Thoracic Surgery, State Key Laboratory of Pharmaceutical Biotechnology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, School of Life Sciences, Nanjing University, Nanjing, China., Xu LT; Department of Cardio-Thoracic Surgery, State Key Laboratory of Pharmaceutical Biotechnology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, School of Life Sciences, Nanjing University, Nanjing, China., Guo XQ; Department of Cardio-Thoracic Surgery, State Key Laboratory of Pharmaceutical Biotechnology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, School of Life Sciences, Nanjing University, Nanjing, China., Zhu XY; Department of Cardio-Thoracic Surgery, State Key Laboratory of Pharmaceutical Biotechnology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, School of Life Sciences, Nanjing University, Nanjing, China., Wang DJ; Department of Cardio-Thoracic Surgery, State Key Laboratory of Pharmaceutical Biotechnology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, School of Life Sciences, Nanjing University, Nanjing, China., Gu HW; Central Laboratory, Nanjing Integrated Traditional Chinese and Western Medicine Hospital Affiliated with Nanjing University of Chinese Medicine, Nanjing, China., Wang XM; Department of Cardio-Thoracic Surgery, State Key Laboratory of Pharmaceutical Biotechnology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, School of Life Sciences, Nanjing University, Nanjing, China. |
| المصدر: | Frontiers in oncology [Front Oncol] 2022 Aug 25; Vol. 12, pp. 959322. Date of Electronic Publication: 2022 Aug 25 (Print Publication: 2022). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101568867 Publication Model: eCollection Cited Medium: Print ISSN: 2234-943X (Print) Linking ISSN: 2234943X NLM ISO Abbreviation: Front Oncol Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation] |
| مستخلص: | Cancer is one of the most serious diseases threatening human health, so it is particularly important to develop effective tumor-targeting drugs. As the first CDK4/6 inhibitor, palbociclib effectively inhibits tumor proliferation by blocking the cell cycle to the G1 phase. 10-HCPT is a Topo I inhibitor; however, its clinical application has been greatly limited due to its high toxicity. Based on the successful development of double target inhibitors, three novel palbociclib derivatives ( HP-1 , HP-2 , and HP-3 ) were designed and synthesized from Palbociclib and 10-HCPT, and their biological activities were investigated. At first, the possible binding sites of the three compounds to Topo I and CDK4/6 were predicted by molecular docking. Then, we evaluated the anti-proliferative effects of the three palbociclib derivatives. In general, human lung cancer cells were more sensitive to HP-1, HP-2, and HP-3, especially NCI-H460. In addition, cell cycle arrest and apoptosis induction were investigated by flow cytometry. The three palbociclib derivatives, especially HP-1, had obvious cell cycle arrest phenomenon on NCI-H460 cells and induced apoptosis of NCI-H460 cells significantly. In the end, it was proved that these three drugs had obvious cyclin-dependent kinase inhibitory activities. In short, all the data showed that HP-1 , HP-2 , and HP-3 could play anti-cancer roles by acting on dual targets and had the characteristics of high efficiencies and low toxicities, which opened up a new idea for the study of palbociclib derivatives. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Li, Zhou, Bai, Zhang, Zhou, Yang, Xu, Guo, Zhu, Wang, Gu and Wang.) |
| References: | Med Res Rev. 1998 Sep;18(5):299-314. (PMID: 9735871) Nat Rev Cancer. 2009 Mar;9(3):153-66. (PMID: 19238148) Eur J Pharm Sci. 2018 Oct 15;123:546-559. (PMID: 30118848) Nat Rev Drug Discov. 2015 Feb;14(2):130-46. (PMID: 25633797) J Biol Chem. 1985 Nov 25;260(27):14873-8. (PMID: 2997227) Breast Cancer Res Treat. 2019 Apr;174(3):615-625. (PMID: 30607633) P T. 2015 Aug;40(8):511-20. (PMID: 26236140) Cancer Chemother Pharmacol. 1998;41(4):257-67. (PMID: 9488594) World J Hepatol. 2015 Apr 18;7(5):787-98. (PMID: 25914779) Cancer Res. 2022 Apr 1;82(7):1170-1171. (PMID: 35373292) Clin Cancer Res. 2016 Apr 15;22(8):2000-8. (PMID: 26631614) Eur J Pharm Sci. 2017 Nov 15;109:65-77. (PMID: 28735042) Cancer Res. 2016 Apr 15;76(8):2301-13. (PMID: 27020857) Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10699-704. (PMID: 9380698) Mol Cancer Ther. 2004 Nov;3(11):1427-38. (PMID: 15542782) |
| فهرسة مساهمة: | Keywords: 10-hydroxy camptothecin; CDK4/6; Topo I; anticancer activity; palbociclib derivatives |
| تواريخ الأحداث: | Date Created: 20220912 Latest Revision: 20220913 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC9453454 |
| DOI: | 10.3389/fonc.2022.959322 |
| PMID: | 36091173 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2234-943X |
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| DOI: | 10.3389/fonc.2022.959322 |