期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 27, 期 10, 页码 2112-2121出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2019.04.009
关键词
Antitumor; Platinum; DNA damage; Coumarin; Cyclooxygenase inhibition
资金
- Natural Science Foundation of Shandong [ZR2017BH092]
- National Natural Science Foundation of China [21807056, 21473085]
- Doctoral Foundation of Liaocheng University [318051635]
- Open Project of Shandong Collaborative Innovation Center for Antibody Drugs [CIC-AD1836, CIC-AD1835]
- Taishan scholar research Foundation
A series of bi-functional 7-hydroxycoumarin platinum(IV) complexes were synthesized, characterized, and evaluated for antitumor activities. The 7-hydroxycoumarin platinum(IV) complexes display moderate to effective antitumor activities toward the tested cell lines and show much potential in overcoming drug resistance of platinum(II) drugs. In reducing microenvironment, the title compounds could be reduced to platinum(II) complex accompanied with two equivalents of coumarin units. By a unique mechanism, the 7-hydroxycoumarin platinum(IV) complex attacks DNA via the released platinum(II) compound, meanwhile it also inhibits the activities of cyclooxygenase by coumarin fragment. This action mechanism might be of much benefit for reducing tumor-related inflammation in the progress of inhibiting tumor proliferation and overcoming cisplatin resistance. The incorporation of 7-hydroxycoumarin leads to significantly enhanced platinum accumulation in both whole tumor cells and DNA. The HSA interaction investigation reveals that the tested coumarin platinum (IV) compound could effectively combine with HSA via van der Waals force and hydrogen bond.
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