Impact of androstane A- and D-ring inversion on 17β-hydroxysteroid dehydrogenase type 3 inhibitory activity, androgenic effect and metabolic stability

Cortés‐Benítez, Francisco; Roy, Jenny; Maltais, René; Poirier, Donald

doi:10.1016/j.bmc.2017.02.008

Cited by 8 publications

(18 citation statements)

References 37 publications

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“…In order to investigate the potential estrogenic profile of the synthesized compounds with the most relevant antiproliferative activities (steroids 2 and 3), their effect on cell growth was measured on the estrogen-sensitive breast cancer T47-D cells (ER + ) in a serum-free culture medium. This proliferative/estrogenic activity was expressed as the difference between the cell proliferation (in percentage) caused by a given compound and the basal cell proliferation fixed at 100% (Figure 3) [44,45]. The natural estrogen E2 was also tested as a reference compound.…”

Section: Cell Growth Effectmentioning

confidence: 99%

Δ 9,11 -Estrone derivatives as potential antiproliferative agents: synthesis, in vitro biological evaluation and docking studies

Canário¹,

Matias²,

Brito³

et al. 2020

Comptes Rendus. Chimie

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A series of ∆ 9,11 -estrone derivatives with A-and D-ring modifications has been synthesized and evaluated as antiproliferative agents. The cytotoxicity was assessed in six cell lines (MCF-7, T47-D, LNCaP, HepaRG, Caco-2 and NHDF) by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and a cell cycle distribution analysis was performed by flow cytometry. Some compounds exhibited relevant cytotoxicity, particularly ∆ 9,11 -estrone, which was the most active against HepaRG cells (IC 50 = 6.67 µM). Besides the relevance of the double bond in the C-ring, the presence of a 16E-benzylidene group increased the antiproliferative effect on MCF-7 and T47-D cells. Moreover, the introduction of iodine in positions 2 and 4 of estrone seemed to induce a selective cytotoxicity for HepaRG cells. Flow cytometry experiments evidenced a 34% reduction of HepaRG cell viability after treatment with ∆ 9,11 -estrone and a cell cycle arrest at the G 0 /G 1 phase. Estrogenic activity was also observed for this compound at 0.1 µM in T47-D cells, and molecular docking studies estimated a marked interaction between this compound and the estrogen receptor α.

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Section: Cell Growth Effectmentioning

confidence: 99%

Δ 9,11 -Estrone derivatives as potential antiproliferative agents: synthesis, in vitro biological evaluation and docking studies

Canário¹,

Matias²,

Brito³

et al. 2020

Comptes Rendus. Chimie

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show abstract

“…To determine the potential estrogenic profile of the synthesized compound with the most relevant anti-proliferative activity (steroid 11 ), its cell growing effect was measured on the estrogen-sensitive breast cancer T47-D cells (ER + ) in serum-free culture medium. This proliferative/estrogenic activity was expressed as the difference between the cell proliferation (in percentage) caused by a given compound and the basal cell proliferation fixed at 100% ( Figure 2 ) [ 35 , 36 ]. E2 was also tested as reference compound.…”

Section: Resultsmentioning

confidence: 99%

New Estrone Oxime Derivatives: Synthesis, Cytotoxic Evaluation and Docking Studies

et al. 2021

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The interest in the introduction of the oxime group in molecules aiming to improve their biological effects is increasing. This work aimed to develop new steroidal oximes of the estrane series with potential antitumor interest. For this, several oximes were synthesized by reaction of hydroxylamine with the 17-ketone of estrone derivatives. Then, their cytotoxicity was evaluated in six cell lines. An estrogenicity assay, a cell cycle distribution analysis and a fluorescence microscopy study with Hoechst 3358 staining were performed with the most promising compound. In addition, molecular docking studies against estrogen receptor α, steroid sulfatase, 17β-hydroxysteroid dehydrogenase type 1 and β-tubulin were also accomplished. The 2-nitroestrone oxime showed higher cytotoxicity than the parent compound on MCF-7 cancer cells. Furthermore, the oximes bearing halogen groups in A-ring evidenced selectivity for HepaRG cells. Remarkably, the Δ9,11-estrone oxime was the most cytotoxic and arrested LNCaP cells in the G2/M phase. Fluorescence microscopy studies showed the presence of condensed DNA typical of prophase and condensed and fragmented nuclei characteristic of apoptosis. However, this oxime promoted the proliferation of T47-D cells. Interestingly, molecular docking studies estimated a strong interaction between Δ9,11-estrone oxime and estrogen receptor α and β-tubulin, which may account for the described effects.

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“…Several groups have developed many of steroids so far, and non-steroidal 17β-HSD3 inhibitors had been also synthesized successively, such as RM-532-105, STX1383 and STX217. 8) They could Chemical and Pharmaceutical Bulletin Advance Publication significantly lower the plasma testosterone levels and inhibit the androgen-dependent tumor growth in vivo. 17β-HSD3 inhibitors have become hopeful drug candidate agent in the treatment of hormone-dependent prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

Preclinical Pharmacokinetics, Tissue Distribution and Primary Safety Evaluation of a Novel Curcumin Analogue H10 Suspension, a Potential 17β Hydroxysteroid Dehydrogenase Type 3 Inhibitor

Xiao¹,

Yu²,

Li³

et al. 2021

CHEMICAL & PHARMACEUTICAL BULLETIN

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Impact of androstane A- and D-ring inversion on 17β-hydroxysteroid dehydrogenase type 3 inhibitory activity, androgenic effect and metabolic stability

Cited by 8 publications

References 37 publications

Δ 9,11 -Estrone derivatives as potential antiproliferative agents: synthesis, in vitro biological evaluation and docking studies

Δ 9,11 -Estrone derivatives as potential antiproliferative agents: synthesis, in vitro biological evaluation and docking studies

New Estrone Oxime Derivatives: Synthesis, Cytotoxic Evaluation and Docking Studies

Preclinical Pharmacokinetics, Tissue Distribution and Primary Safety Evaluation of a Novel Curcumin Analogue H10 Suspension, a Potential 17β Hydroxysteroid Dehydrogenase Type 3 Inhibitor

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