Are Pt(IV) Prodrugs That Release Combretastatin A4 True Multi-action Prodrugs?
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F21%3A00554721" target="_blank" >RIV/68081707:_____/21:00554721 - isvavai.cz</a>
Alternative codes found
RIV/61989592:15310/21:73609722
Result on the web
<a href="https://pubs.acs.org/doi/10.1021/acs.jmedchem.1c00706" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.jmedchem.1c00706</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.jmedchem.1c00706" target="_blank" >10.1021/acs.jmedchem.1c00706</a>
Alternative languages
Result language
angličtina
Original language name
Are Pt(IV) Prodrugs That Release Combretastatin A4 True Multi-action Prodrugs?
Original language description
Multi-action Pt(IV) derivatives of cisplatin with combretastatin A4 (CA4) bioactive ligands that are conjugated to Pt(IV) by carbonate are unique because the ligand (IC50 < 10 nM) is dramatically 1000-folds more cytotoxic than cisplatin in vitro. The Pt(IV)-CA4 prodrugs were as cytotoxic as CA4 itself, indicating that the platinum moiety probably plays an insignificant role in triggering cytotoxicity, suggesting that the Pt(IV)-CA4 complexes act as prodrugs for CA4 rather than as true multi-action prodrugs. In vivo tests (Lewis lung carcinoma) show that ctc-[Pt(NH3)(2)(PhB)(CA4)Cl-2] inhibited tumor growth by 93% compared to CA4 (67%), cisplatin (84%), and 1:1:1 cisplatin/CA4/PhB (85%) while displaying <5% body weight loss compared to cisplatin (20%) or CA4 (10%). In this case, and perhaps with other extremely potent bioactive ligands, platinum(IV) acts merely as a self-immolative carrier triggered by reduction in the cancer cell with only a minor contribution to cytotoxicity.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30104 - Pharmacology and pharmacy
Result continuities
Project
<a href="/en/project/GA21-27514S" target="_blank" >GA21-27514S: Metal-based compounds for enhanced cancer immunotherapy</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Medicinal Chemistry
ISSN
0022-2623
e-ISSN
1520-4804
Volume of the periodical
64
Issue of the periodical within the volume
15
Country of publishing house
US - UNITED STATES
Number of pages
15
Pages from-to
11364-11378
UT code for WoS article
000685644300047
EID of the result in the Scopus database
2-s2.0-85113672481