Ring-Contracted Artemisinin Derivatives as Novel CDK 4/6 Inhibitors: Synthesis and Anti-Breast Cancer Evaluation
Abstract
The endoperoxide group of artemisinins is universally accepted an essential group for their anti-cancer effects. In this study, a series of D-ring-contracted artemisinin derivatives were constructed by combining ring-contracted artemisinin core with fragments of functional heterocyclic molecules or classical CDK4/6 inhibitors to identify more efficacious breast cancer treatment agents. Twenty-six novel hybridized molecules were synthesized and characterized by HRMS, IR, 1H-NMR and 13C NMR. In antiproliferative activities and kinase inhibitory effects assays, we found that the antiproliferative effects of B01 were close to those of the positive control Palbociclib, with GI50 values of 4.87±0.23 μM and 9.97±1.44 μM towards T47D cells and MDA-MB-436 cells respectively. In addition, the results showed that B01 was the most potent compound against CDK6/cyclin D3 kinase, with an IC50 value of 0.135±0.041 μM, and its activity was approximately 1/3 of the positive control Palbociclib.
Graphical Abstract
Conflict of interests
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are openly available in RING-CONTRACTED ARTEMMISININ DERIVATIVES AS NOVEL CDK4/6 INHIBITORS : SYNTHRSIS AND ANTI-BREAST CANCER EVALUATION at https://doi.org/10.1002/cbdv.20240109, reference number 20240109.
