-
Something wrong with this record ?
Platinum(IV)-Estramustine Multiaction Prodrugs Are Effective Antiproliferative Agents against Prostate Cancer Cells
S. Karmakar, H. Kostrhunova, T. Ctvrtlikova, V. Novohradsky, D. Gibson, V. Brabec
Language English Country United States
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Cisplatin chemistry MeSH
- Estramustine chemistry MeSH
- Humans MeSH
- Tumor Cells, Cultured MeSH
- Prostatic Neoplasms drug therapy pathology MeSH
- Prodrugs chemistry pharmacology MeSH
- Antineoplastic Agents chemistry pharmacology MeSH
- Drug Screening Assays, Antitumor MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Herein, we describe the synthesis, characterization, and biological properties of Pt(IV) derivatives of cisplatin with estramustine at the first axial position, which is known to disrupt the microtubule assembly and act as an androgen antagonist, and varying the second axial position using an innocent ligand (acetate or hydroxyl) to prepare dual-action and triple-action prodrugs with known inhibitors of histone deacetylase, cyclooxygenase, and pyruvate dehydrogenase kinase. We demonstrate superior antiproliferative activity at submicromolar concentrations of the prodrugs against a panel of cancer cell lines, particularly against prostate cancer cell lines. The results obtained in this study exemplify the complex mode of action of "multiaction" Pt(IV) prodrugs. Interestingly, changing the second axial ligand in the Pt-estramustine complex has a significant effect on the mode of action, suggesting that all three components of the Pt(IV) prodrugs (platinum moiety and axial ligands) contribute to the killing of cells and not just one dominant component.
References provided by Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc21011846
- 003
- CZ-PrNML
- 005
- 20210507103243.0
- 007
- ta
- 008
- 210420s2020 xxu f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1021/acs.jmedchem.0c01400 $2 doi
- 035 __
- $a (PubMed)33175515
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a xxu
- 100 1_
- $a Karmakar, Subhendu $u Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel
- 245 10
- $a Platinum(IV)-Estramustine Multiaction Prodrugs Are Effective Antiproliferative Agents against Prostate Cancer Cells / $c S. Karmakar, H. Kostrhunova, T. Ctvrtlikova, V. Novohradsky, D. Gibson, V. Brabec
- 520 9_
- $a Herein, we describe the synthesis, characterization, and biological properties of Pt(IV) derivatives of cisplatin with estramustine at the first axial position, which is known to disrupt the microtubule assembly and act as an androgen antagonist, and varying the second axial position using an innocent ligand (acetate or hydroxyl) to prepare dual-action and triple-action prodrugs with known inhibitors of histone deacetylase, cyclooxygenase, and pyruvate dehydrogenase kinase. We demonstrate superior antiproliferative activity at submicromolar concentrations of the prodrugs against a panel of cancer cell lines, particularly against prostate cancer cell lines. The results obtained in this study exemplify the complex mode of action of "multiaction" Pt(IV) prodrugs. Interestingly, changing the second axial ligand in the Pt-estramustine complex has a significant effect on the mode of action, suggesting that all three components of the Pt(IV) prodrugs (platinum moiety and axial ligands) contribute to the killing of cells and not just one dominant component.
- 650 _2
- $a protinádorové látky $x chemie $x farmakologie $7 D000970
- 650 _2
- $a cisplatina $x chemie $7 D002945
- 650 _2
- $a screeningové testy protinádorových léčiv $7 D004354
- 650 _2
- $a estramustin $x chemie $7 D004961
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a mužské pohlaví $7 D008297
- 650 _2
- $a prekurzory léčiv $x chemie $x farmakologie $7 D011355
- 650 _2
- $a nádory prostaty $x farmakoterapie $x patologie $7 D011471
- 650 _2
- $a nádorové buňky kultivované $7 D014407
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a práce podpořená grantem $7 D013485
- 700 1_
- $a Kostrhunova, Hana $u Institute of Biophysics, Czech Academy of Sciences, Kralovopolska 135, Brno CZ-61265, Czech Republic
- 700 1_
- $a Ctvrtlikova, Tereza $u Institute of Biophysics, Czech Academy of Sciences, Kralovopolska 135, Brno CZ-61265, Czech Republic
- 700 1_
- $a Novohradsky, Vojtech $u Institute of Biophysics, Czech Academy of Sciences, Kralovopolska 135, Brno CZ-61265, Czech Republic
- 700 1_
- $a Gibson, Dan $u Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel
- 700 1_
- $a Brabec, Viktor $u Institute of Biophysics, Czech Academy of Sciences, Kralovopolska 135, Brno CZ-61265, Czech Republic
- 773 0_
- $w MED00010049 $t Journal of medicinal chemistry $x 1520-4804 $g Roč. 63, č. 22 (2020), s. 13861-13877
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/33175515 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y p $z 0
- 990 __
- $a 20210420 $b ABA008
- 991 __
- $a 20210507103242 $b ABA008
- 999 __
- $a ok $b bmc $g 1650271 $s 1132225
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2020 $b 63 $c 22 $d 13861-13877 $e 20201111 $i 1520-4804 $m Journal of medicinal chemistry $n J Med Chem $x MED00010049
- LZP __
- $a Pubmed-20210420
