Bibliographic Details
| Title: |
Design, synthesis, and anticancer activity of three novel palbociclib derivatives |
| Authors: |
Tian Li, An-Di Zhou, Li-Fei Bai, Xiao-Yang Zhang, Yu-Ting Zhou, Hai-Li Yang, Le-Tian Xu, Xin-Qin Guo, Xi-Yu Zhu, Dong-Jin Wang, Hong-Wei Gu, Xiao-Ming Wang |
| Source: |
Frontiers in Oncology, Vol 12 (2022) |
| Publisher Information: |
Frontiers Media S.A., 2022. |
| Publication Year: |
2022 |
| Collection: |
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| Subject Terms: |
palbociclib derivatives, anticancer activity, CDK4/6, 10-hydroxy camptothecin, Topo I, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2234-943X |
| Relation: |
https://www.frontiersin.org/articles/10.3389/fonc.2022.959322/full; https://doaj.org/toc/2234-943X |
| DOI: |
10.3389/fonc.2022.959322 |
| Access URL: |
https://doaj.org/article/f84a13e460654bdda28d27d01158d95b |
| Accession Number: |
edsdoj.f84a13e460654bdda28d27d01158d95b |
| Database: |
Directory of Open Access Journals |
