Novel series of 17β-pyrazolylandrosta-5,16-diene derivatives and their inhibitory effect on 17α-hydroxylase/C17,20-lyase

Iványi, Zoltán; Szabó, Nikoletta; Wölfling, János; Szécsi, Mihály; Julesz, J.; Schneider, Gyula

doi:10.1016/j.steroids.2012.07.001

Cited by 15 publications

(7 citation statements)

References 25 publications

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“…galeterone) for the treatment of prostate cancers. 27,28 Previously [29][30][31] we reported a series of C17-exo-heterocyclic androstanes as potential inhibitors of aromatase (CYP19) and/or CYP17. 32,33 Based on these and other studies, the geometry of the C17 heterocyclic ring and the location of heteroatoms such as N, S or O appear critical for inhibition, likely due to coordinate interactions between inhibitor and the heme iron of CYP17.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of A-ring fused pyridine d-modified androstane derivatives for antiproliferative and aldo–keto reductase 1C3 inhibitory activity

et al. 2018

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New A-ring pyridine fused androstanes in 17a-homo-17-oxa (d-homo lactone), 17α-picolyl or 17()-picolinylidene series were synthesized and validated by X-ray crystallography, HRMS, IR and NMR spectroscopy. Novel compounds ,, and were prepared by treatment of 4-en-3-one or 4-ene-3,6-dione d-modified androstane derivatives with propargylamine catalyzed by Cu(ii), and evaluated for potential anticancer activity using human cancer cell lines and recombinant targets of steroidal anti-cancer drugs. Pyridine fusion to position 3,4 of the A-ring may dramatically enhance affinity of 17α-picolyl compounds for CYP17 while conferring selective antiproliferative activity against PC-3 cells. Similarly, pyridine fusion to the A-ring of steroidal d-homo lactones led to identification of new inhibitors of aldo-keto reductase 1C3, an enzyme targeted in acute myeloid leukemia, breast and prostate cancers. One A-pyridine d-lactone steroid also has selective submicromolar antiproliferative activity against HT-29 colon cancer cells. None of the new derivatives have affinity for estrogen or androgen receptors in a yeast screen, suggesting negligible estrogenicity and androgenicity. Combined, our results suggest that A-ring pyridine fusions have potential in modulating the anticancer activity of steroidal compounds.

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Section: Introductionmentioning

confidence: 99%

Evaluation of A-ring fused pyridine d-modified androstane derivatives for antiproliferative and aldo–keto reductase 1C3 inhibitory activity

et al. 2018

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“…В работе [51] были получены стероидные N-aцетилированные пиразолины, различающиеся конфигурацией атома С5¢ в гетероцикле (174-185) (формула 21).…”

Section: производные и аналоги абиратерона и галетеронаunclassified

Steroidal Inhibitors of CYP17A1 as a Template For Novel Anti-Cancer Agents Development

Latysheva

Misharin

2018

BMCRM

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This review deals with studies of researches of novel CYP17A1 steroidal inhibitors and relative compounds published over the last ten years. The review contains six chapters in which novel targets of well-known CYP17A1 inhibirors (abiraterone and galeterone), anti-cancer and anti-proliferative activities of them major metabolites and new synthetic analogs, and in addition another nitrogen-containing androstane and pregnane derivatives are considered. In the review 354 structures of novel steroid derivatives and them anti-cancer efficiency data are considered. Analysis of the literature data allows us to consider steroidal inhibitors of CYP17A1 as multi-target anti-cancer agents with high pharmacological potential.

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“…In the case of the 17α-azido compound pair, the Δ 4 -3-oxo derivative proved to be more effective compared to the Δ 5 -3-hydroxy. This is against the general tendency that 17-heterocyclic inhibitors based on a progesterone scaffold are normally weaker than the corresponding pregnenolone analogs [Iványi et al 2012;Njar et al 1998], but corresponds to other earlier examples found among 17β-oxazolidones and 17β-oxazolines [Ondré et al 2008;Ondré et al 2009]. The IC50 parameter of the most effective 17β-azido-androst-5-en-3β-ol GT-101 indicates a 2.5-fold stronger binding compared to the substrate, and its inhibitory potential was found close to that of the nonsteroidal imidazole reference ketoconazole.…”

Section: -Azido Androstenesmentioning

confidence: 97%

In vitro inhibition of the estrogen biosynthesis enzyme system with new steroid derivatives

Herman

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Novel series of 17β-pyrazolylandrosta-5,16-diene derivatives and their inhibitory effect on 17α-hydroxylase/C17,20-lyase

Cited by 15 publications

References 25 publications

Evaluation of A-ring fused pyridine d-modified androstane derivatives for antiproliferative and aldo–keto reductase 1C3 inhibitory activity

Evaluation of A-ring fused pyridine d-modified androstane derivatives for antiproliferative and aldo–keto reductase 1C3 inhibitory activity

Steroidal Inhibitors of CYP17A1 as a Template For Novel Anti-Cancer Agents Development

In vitro inhibition of the estrogen biosynthesis enzyme system with new steroid derivatives

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