Missing Selectivity of Targeted 4β-Phorbol Prodrugs Expected to be Potential Chemotherapeutics
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22330%2F20%3A43918199" target="_blank" >RIV/60461373:22330/20:43918199 - isvavai.cz</a>
Result on the web
<a href="https://pubs.acs.org/doi/10.1021/acsmedchemlett.9b00554" target="_blank" >https://pubs.acs.org/doi/10.1021/acsmedchemlett.9b00554</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acsmedchemlett.9b00554" target="_blank" >10.1021/acsmedchemlett.9b00554</a>
Alternative languages
Result language
angličtina
Original language name
Missing Selectivity of Targeted 4β-Phorbol Prodrugs Expected to be Potential Chemotherapeutics
Original language description
Targeting cytotoxic 4β-phorbol esters toward cancer tissue was attempted by conjugating a 4β-pborbol derivative with substrates for the proteases prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) expressed in cancer tissue. The hydrophilic peptide moiety was hypothesized to prevent penetration of the prodrugs into cells and prevent interaction with PKC. Cleavage of the peptide in cancer tumors was envisioned to release lipophilic cytotoxins, which subsequently penetrate into cancer cells. The 4β-phorbol esters were prepared from 4β-phorbol isolated from Croton tiglium seeds, while the peptides were prepared by solid-phase synthesis. Cellular assays revealed activation of PKC by the prodrugs and efficient killing of both peptidase positive as well as peptidase negative cells. Consequently no selectivity for enzyme expressing cells was found.
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
30107 - Medicinal chemistry
Result continuities
Project
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Continuities
S - Specificky vyzkum na vysokych skolach
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
ACS Medicinal Chemistry Letters
ISSN
1948-5875
e-ISSN
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Volume of the periodical
11
Issue of the periodical within the volume
5
Country of publishing house
US - UNITED STATES
Number of pages
7
Pages from-to
671-677
UT code for WoS article
000535281200011
EID of the result in the Scopus database
2-s2.0-85077646261