Synthesis and Structure–Activity Relationships of Novel Non-Steroidal CYP17A1 Inhibitors as Potential Prostate Cancer Agents

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Standard

Synthesis and Structure–Activity Relationships of Novel Non-Steroidal CYP17A1 Inhibitors as Potential Prostate Cancer Agents. / Wróbel, Tomasz M.; Rogova, Oksana; Sharma, Katyayani; Velazquez, Maria Natalia Rojas; Pandey, Amit V.; Jørgensen, Flemming Steen; Arendrup, Frederic S.; Andersen, Kasper L.; Björkling, Fredrik.

I: Biomolecules, Bind 12, Nr. 2, 165, 2022.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Wróbel, TM, Rogova, O, Sharma, K, Velazquez, MNR, Pandey, AV, Jørgensen, FS, Arendrup, FS, Andersen, KL & Björkling, F 2022, 'Synthesis and Structure–Activity Relationships of Novel Non-Steroidal CYP17A1 Inhibitors as Potential Prostate Cancer Agents', Biomolecules, bind 12, nr. 2, 165. https://doi.org/10.3390/biom12020165

APA

Wróbel, T. M., Rogova, O., Sharma, K., Velazquez, M. N. R., Pandey, A. V., Jørgensen, F. S., Arendrup, F. S., Andersen, K. L., & Björkling, F. (2022). Synthesis and Structure–Activity Relationships of Novel Non-Steroidal CYP17A1 Inhibitors as Potential Prostate Cancer Agents. Biomolecules, 12(2), [165]. https://doi.org/10.3390/biom12020165

Vancouver

Wróbel TM, Rogova O, Sharma K, Velazquez MNR, Pandey AV, Jørgensen FS o.a. Synthesis and Structure–Activity Relationships of Novel Non-Steroidal CYP17A1 Inhibitors as Potential Prostate Cancer Agents. Biomolecules. 2022;12(2). 165. https://doi.org/10.3390/biom12020165

Author

Wróbel, Tomasz M. ; Rogova, Oksana ; Sharma, Katyayani ; Velazquez, Maria Natalia Rojas ; Pandey, Amit V. ; Jørgensen, Flemming Steen ; Arendrup, Frederic S. ; Andersen, Kasper L. ; Björkling, Fredrik. / Synthesis and Structure–Activity Relationships of Novel Non-Steroidal CYP17A1 Inhibitors as Potential Prostate Cancer Agents. I: Biomolecules. 2022 ; Bind 12, Nr. 2.

Bibtex

@article{53e5988f59f5461b9b5c5c7d9ad08fe1,
title = "Synthesis and Structure–Activity Relationships of Novel Non-Steroidal CYP17A1 Inhibitors as Potential Prostate Cancer Agents",
abstract = "Twenty new compounds, targeting CYP17A1, were synthesized, based on our previous work on a benzimidazole scaffold, and their biological activity evaluated. Inhibition of CYP17A1 is an important modality in the treatment of prostate cancer, which remains the most abundant cancer type in men. The biological assessment included CYP17A1 hydroxylase and lyase inhibition, CYP3A4 and P450 oxidoreductase (POR) inhibition, as well as antiproliferative activity in PC3 prostate cancer cells. The most potent compounds were selected for further analyses including in silico modeling. This combined effort resulted in a compound (comp 2, IC50 1.2 µM, in CYP17A1) with a potency comparable to abiraterone and selectivity towards the other targets tested. In addition, the data provided an understanding of the structure–activity relationship of this novel non-steroidal compound class.",
keywords = "CYP17A1, Cytochrome P450 17A1, Enzyme inhibition, Prostate cancer",
author = "Wr{\'o}bel, {Tomasz M.} and Oksana Rogova and Katyayani Sharma and Velazquez, {Maria Natalia Rojas} and Pandey, {Amit V.} and J{\o}rgensen, {Flemming Steen} and Arendrup, {Frederic S.} and Andersen, {Kasper L.} and Fredrik Bj{\"o}rkling",
note = "Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2022",
doi = "10.3390/biom12020165",
language = "English",
volume = "12",
journal = "Biomolecules",
issn = "2218-273X",
publisher = "MDPI",
number = "2",

}

RIS

TY - JOUR

T1 - Synthesis and Structure–Activity Relationships of Novel Non-Steroidal CYP17A1 Inhibitors as Potential Prostate Cancer Agents

AU - Wróbel, Tomasz M.

AU - Rogova, Oksana

AU - Sharma, Katyayani

AU - Velazquez, Maria Natalia Rojas

AU - Pandey, Amit V.

AU - Jørgensen, Flemming Steen

AU - Arendrup, Frederic S.

AU - Andersen, Kasper L.

AU - Björkling, Fredrik

N1 - Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022

Y1 - 2022

N2 - Twenty new compounds, targeting CYP17A1, were synthesized, based on our previous work on a benzimidazole scaffold, and their biological activity evaluated. Inhibition of CYP17A1 is an important modality in the treatment of prostate cancer, which remains the most abundant cancer type in men. The biological assessment included CYP17A1 hydroxylase and lyase inhibition, CYP3A4 and P450 oxidoreductase (POR) inhibition, as well as antiproliferative activity in PC3 prostate cancer cells. The most potent compounds were selected for further analyses including in silico modeling. This combined effort resulted in a compound (comp 2, IC50 1.2 µM, in CYP17A1) with a potency comparable to abiraterone and selectivity towards the other targets tested. In addition, the data provided an understanding of the structure–activity relationship of this novel non-steroidal compound class.

AB - Twenty new compounds, targeting CYP17A1, were synthesized, based on our previous work on a benzimidazole scaffold, and their biological activity evaluated. Inhibition of CYP17A1 is an important modality in the treatment of prostate cancer, which remains the most abundant cancer type in men. The biological assessment included CYP17A1 hydroxylase and lyase inhibition, CYP3A4 and P450 oxidoreductase (POR) inhibition, as well as antiproliferative activity in PC3 prostate cancer cells. The most potent compounds were selected for further analyses including in silico modeling. This combined effort resulted in a compound (comp 2, IC50 1.2 µM, in CYP17A1) with a potency comparable to abiraterone and selectivity towards the other targets tested. In addition, the data provided an understanding of the structure–activity relationship of this novel non-steroidal compound class.

KW - CYP17A1

KW - Cytochrome P450 17A1

KW - Enzyme inhibition

KW - Prostate cancer

U2 - 10.3390/biom12020165

DO - 10.3390/biom12020165

M3 - Journal article

C2 - 35204665

AN - SCOPUS:85122924205

VL - 12

JO - Biomolecules

JF - Biomolecules

SN - 2218-273X

IS - 2

M1 - 165

ER -

ID: 290596423