Aim: In spite of the availability of different chemotherapies for cancer treatment, there is still a need for new candidates with higher efficacy and lower toxicity.
Methodology: Aurones 7a-f, 8a-f and furoaurones 13a-f, 16a-c were synthesized. Some compounds were selected by the National Cancer Institute, USA, for cytotoxicity screening.
Results & discussion: The furoaurone derivative, 13a was the most active one exhibiting promising growth inhibition against leukemia, K562 and melanoma, MDA-MB-435 cells at concentration of 10 μM. It induced apoptosis in both cell lines by activation of CASP3 and inhibition of CDK2. Additionally, 13a showed good selectivity over normal kidney and liver cells. Simulation docking study was undertaken to gain insight into the possible binding mode of 13a in the CDK2 enzyme.
Conclusion: The furoaurone 13a can be considered as a scaffold for further optimization to obtain more active hits. Graphical abstract [Formula: see text].
Keywords: CDK2; apoptosis; aurones; cytotoxicity; furoaurones.