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Conclusions
In summary, using structure-based design approach, we have
successfully designed and synthesized a novel series of 2,3-
dihydroimidazo [1,2-c]quinazoline with a hydroxamate group
essential for chelation with the zinc ion in the active site of
HDAC as novel PI3K/HDAC dual inhibitors. As expected, most
of compounds exhibited distinct high to moderate inhibitory
activities against both HDAC1 and PI3Ka. Moreover, the selec-
tivity assay of compounds 12b, 12c and 12e shows that they are
excellent pan inhibitors for HDACs and PI3Ks. In addition,
compound 12e showed the most potent inhibitory activity
against K562 and Hut78. By combining two distinct pharma-
cophores into one molecule, we have demonstrated the example
of PI3K/HDAC dual inhibitors as a promising approach to
search for efficient anticancer multi-target agents.
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There are no conicts to declare.
Acknowledgements
This study was supported by the National Natural Science
Foundation of China (Grant No. 81673301) and Fundamental
Research Funds for the Central Universities (Grant No.
3010050069).
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