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A potent aminonaphthalimide platinum(IV) complex with effective antitumor activities in vitro and in vivo displaying dual DNA damage effects on tumor cells.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2019 Oct 15; Vol. 29 (20), pp. 126670. Date of Electronic Publication: 2019 Sep 04. - Publication Year :
- 2019
-
Abstract
- A new aminonaphthalimide platinum(IV) complex was developed by incorporating aminonaphthalimide, a DNA intercalator, into the platinum(IV) system. This complex displayed potent antitumor activities against all tested tumor cell lines in vitro and showed great potential in overcoming drug resistance of cisplatin. Moreover, it remarkably inhibited the growth of CT26 xenografts in BALB/c mice without severe side effects in vivo. Then, the compound exhibited a dual DNA damage antitumor mechanism that it could interact with DNA in tetravalent form via the naphthalimide group to cause DNA lesion, and the further liberation of platinum(II) complex after reduction would induce remarkable secondary damage to DNA. Meanwhile, it caused cell apoptosis through an intrinsic apoptosis pathway by up-regulating the expression of caspase 3 and caspase 9.<br /> (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Antineoplastic Agents pharmacology
Apoptosis drug effects
Caspases, Initiator genetics
Caspases, Initiator metabolism
Cell Line, Tumor
Cisplatin pharmacology
Coordination Complexes pharmacology
DNA drug effects
DNA Damage
Drug Resistance, Neoplasm
Drug Screening Assays, Antitumor
Gene Expression Regulation drug effects
Heterografts
Humans
Mice
Mice, Inbred BALB C
Neoplasms, Experimental
Signal Transduction
Antineoplastic Agents chemistry
Coordination Complexes chemistry
Naphthalimides chemistry
Organoplatinum Compounds chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 29
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 31500997
- Full Text :
- https://doi.org/10.1016/j.bmcl.2019.126670