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Synthesis and evaluation of bi-functional 7-hydroxycoumarin platinum(IV) complexes as antitumor agents.
- Source :
-
Bioorganic & medicinal chemistry [Bioorg Med Chem] 2019 May 15; Vol. 27 (10), pp. 2112-2121. Date of Electronic Publication: 2019 Apr 06. - Publication Year :
- 2019
-
Abstract
- 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.<br /> (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Subjects :
- Antineoplastic Agents metabolism
Antineoplastic Agents pharmacology
Apoptosis drug effects
Cell Line, Tumor
Cell Survival drug effects
Coordination Complexes metabolism
Coordination Complexes pharmacology
Cyclooxygenase 2 chemistry
Cyclooxygenase 2 metabolism
DNA Damage drug effects
Humans
Protein Binding
Serum Albumin chemistry
Serum Albumin metabolism
Antineoplastic Agents chemical synthesis
Coordination Complexes chemical synthesis
Platinum chemistry
Umbelliferones chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3391
- Volume :
- 27
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 30981607
- Full Text :
- https://doi.org/10.1016/j.bmc.2019.04.009