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Development of a series of 4-hydroxycoumarin platinum(IV) hybrids as antitumor agents: Synthesis, biological evaluation and action mechanism investigation.
- Source :
-
Journal of inorganic biochemistry [J Inorg Biochem] 2019 May; Vol. 194, pp. 34-43. Date of Electronic Publication: 2019 Feb 23. - Publication Year :
- 2019
-
Abstract
- A series of new 4-hydroxycoumarin platinum(IV) complexes were designed, synthesized and evaluated as antitumor agents. All the title compounds display moderate to effective antitumor activities toward the tested cell lines and two prominent compounds were screened out with activities comparable to cisplatin and oxaliplatin. The mechanism investigation demonstrates that the platinum(IV) compounds could be reduced to bivalence and exert significant genotoxicity to tumor cells. Meanwhile the coumarin moiety endows the title compounds with cyclooxygenase inhibitory competence which might favour the reduction of tumor-related inflammation and further influence tumor proliferation. The coumarin platinum(IV) complex could effectively induce apoptosis of SKOV-3 cells through up-regulating the expression of caspase3 and caspase9. Furthermore, the conversion of platinum(II) drugs to platinum(IV) form via the conjunction with 4-hydroxycoumarin enhances the drug uptake in whole cells and DNA simultaneously. Moreover, the 4-hydroxycoumarin platinum(IV) complex could combine with human serum albumin via van der Waals force and hydrogen bond, which would influence their transport and bioactivities in vivo.<br /> (Copyright © 2019. Published by Elsevier Inc.)
- Subjects :
- 4-Hydroxycoumarins chemical synthesis
4-Hydroxycoumarins metabolism
Antineoplastic Agents chemical synthesis
Antineoplastic Agents metabolism
Apoptosis drug effects
Cell Line, Tumor
Coordination Complexes chemical synthesis
Coordination Complexes metabolism
Cyclooxygenase 2 Inhibitors chemical synthesis
Cyclooxygenase 2 Inhibitors metabolism
Cyclooxygenase 2 Inhibitors pharmacology
DNA drug effects
DNA Damage drug effects
Drug Design
Drug Screening Assays, Antitumor
HEK293 Cells
Humans
Platinum chemistry
Serum Albumin, Human metabolism
4-Hydroxycoumarins pharmacology
Antineoplastic Agents pharmacology
Coordination Complexes pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3344
- Volume :
- 194
- Database :
- MEDLINE
- Journal :
- Journal of inorganic biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 30826588
- Full Text :
- https://doi.org/10.1016/j.jinorgbio.2019.02.011