Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Human aldo-keto reductase 1C3 (AKR1C3) is a steroid modifying enzyme involved in cancer progression. Here, A-ring modified 17α-picolyl and 17()-picolinylidene androstane derivatives are shown to inhibit AKR1C3 activity . None of the androstane derivatives have off-target affinity for the androgen receptor, based on a fluorescence assay in yeast cells. The X-ray structure of AKR1C3 in complex with the strongest inhibitor, a 17α-picolyl androstane with a C3-oxime modification, was determined at 1.7 Å resolution. Based on this crystal structure and molecular docking, inhibition of AKR1C3 by the 17α-picolyl or 17()-picolinylidene derivatives depends on interactions between the C3 modification and the NADP cofactor, while the C17α-picolyl or C17-picolinylidene group anchors the inhibitor to AKR1C3. Because one AKR1C3 inhibitor identified here was also previously reported to inhibit CYP17, it may be possible for future researchers to design dual AKR1C3/CYP17 inhibitors based on a steroid scaffold for potential treatment of advanced prostate cancers.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12412325 | PMC |
| http://dx.doi.org/10.1080/14756366.2025.2551979 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Toward steroidal anticancer drugs: Non-parametric and 3D-QSAR modeling of 17-picolyl and 17-picolinylidene androstanes with antiproliferative activity on breast adenocarcinoma cells.
J Mol Graph Model
March 2019
University of Novi Sad, Faculty of Sciences, Department of Chemistry, Biochemistry and Environmental Protection, Trg Dositeja Obradovića 3, 21000, Novi Sad, Serbia.
Article Synopsis
- The study focuses on analyzing the lipophilicity and ADMET profiles of a series of androstane derivatives to understand their potential as antiproliferative agents against breast adenocarcinoma cells.
- It employs 3D-QSAR and ligand-based pharmacophore modeling techniques to predict the compounds' effects and identify key structural features that enhance their anticancer activity.
- The findings aim to guide the design and synthesis of new, effective androstane derivatives, providing a framework for developing potential anticancer drugs.
Non-linear assessment of anticancer activity of 17-picolyl and 17-picolinylidene androstane derivatives--chemometric guidelines for further syntheses.
Eur J Pharm Sci
October 2014
University of Novi Sad, Faculty of Sciences, Department of Chemistry, Biochemistry and Environmental Protection, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia.
The present paper deals with prediction of cytotoxic activity of 17-picolyl and 17-picolinylidene androstane derivatives toward androgen receptor negative prostate cancer cell line (PC-3). The prediction was achieved applying artificial neural networks (ANNs) method on the basis of molecular descriptors. The most important descriptors (skin permeability (SP), Madin-Darby canine kidney cell permeability (MDCK) and universal salt solubility factor (S+SF)) were selected by using stepwise selection coupled with partial least squares method.
View Article and Find Full Text PDFSynthesis and cytotoxic activity of some 17-picolyl and 17-picolinylidene androstane derivatives.
Eur J Med Chem
August 2012
Department of Chemistry, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia.
New 17-picolyl and 17-picolinylidene androstane derivatives, 3-10, 15, 18, 19, 22 and 23, were synthesized starting from 17α-picolyl-androst-5-en-3β,17β-diol (1) and 17(Z)-picolinylidene-androst-5-en-3β-ol (2). Reaction of 1 with m-chloroperoxybenzoic acid gives 5α,6α-epoxy N-oxide derivative 3, or, with Jones reagent, 3,6-dione derivative 4; while 17α-picolyl-androst-5-en-3β,4α,17β-triol (5) or 3β,4β,17β-triol (6) derivatives are obtainable from 1 using SeO(2) in dioxane. Base-catalyzed tosyl group elimination from 7 or 9 affords AB conjugated derivatives 8 and 10.
View Article and Find Full Text PDFSynthesis of some epoxy and/or N-oxy 17-picolyl and 17-picolinylidene-androst-5-ene derivatives and evaluation of their biological activity.
Steroids
January 2008
Department of Chemistry, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, 21 000 Novi Sad, Serbia.
Steroidal epoxy and/or N-oxy 17-picolyl and 17-picolinylidene-androst-5-ene derivatives have been prepared using 3beta,17beta-dihydroxy-17alpha-picolyl-androst-5-ene (1), 3beta-acetoxy-17-picolinylidene-androst-5-ene (2), and 3beta-hydroxy-17-picolinylidene-androst-5-ene (3) as synthetic precursors. The compounds 2 and/or 3 were reacted with m-chloroperoxybenzoic acid (MCPBA). The compounds synthesized from 2 were 17-picolinylidene-N-oxide 4, 5alpha,6alpha-epoxy and 5beta,6beta-epoxy-17-picolinylidene-N-oxide 5 and 6, and 5alpha,6alpha:17alpha,20alpha- and 5beta,6beta:17alpha,20alpha-diepoxy-N-oxide 7 and 8.
View Article and Find Full Text PDFSynthesis and biological evaluation of some 17-picolyl and 17-picolinylidene androst-5-ene derivatives.
Steroids
January 2007
Department of Chemistry, Faculty of Sciences, University of Novi Sad, 21000 Novi Sad, Trg Dositeja Obradovića 3, Serbia.
Starting from dehydroepiandrosterone (1) 17-picolyl (2), 17-picolinylidene (7), 17-picolinylidene-16-one (10 and 11), and 17-picolyl-16-one (15) derivatives of androst-5-ene were synthesized in one, two, four and five steps respectively. By the Oppenauer oxidation or dehydration of 2, 7, 10, and 11 with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), the corresponding A and B ring modified derivatives 3, 5, 6, 8, 9, and 12-14 were obtained. The structure of 2 was unambiguously proved by the appropriate X-ray structural analysis.
View Article and Find Full Text PDF