Design, synthesis and biological evaluation of new steroidal β-triazoly enones as potent antiproliferative agents

Zhao, Jianwei; Guo, Jiawen; Minyuan, Huang; You, Ya-Zhen; Wu, Zeng-Hui; Liu, Hong‐Min; Huang, Le Hui

doi:10.1016/j.steroids.2019.108431

Cited by 14 publications

(9 citation statements)

References 21 publications

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“…The synthesis of the intermediates is shown in Scheme 1 . Compounds 1a–1j were obtained by diazotization and azide reactions of various anilines ( Zhao et al, 2019 ). Then, a click reaction between intermediates 1a–1j and propynol gave compounds 2a–2j ( Luan et al, 2019 ).…”

Section: Resultsmentioning

confidence: 99%

Synthesis and evaluation of anticancer activity of quillaic acid derivatives: A cell cycle arrest and apoptosis inducer through NF-κB and MAPK pathways

et al. 2022

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A series of quillaic acid derivatives with different substituents on the 28-carboxyl group were designed and synthesized. Five human cancer cell lines (HCT116, BEL7402, HepG2, SW620, and MCF-7) were evaluated for their antitumor activity in vitro. Some of the tested derivatives showed improved antiproliferative activity compared to the lead compound, quillaic acid. Among them, compound E (IC50 = 2.46 ± 0.44 μM) showed the strongest antiproliferative activity against HCT116 cells; compared with quillaic acid (IC50 > 10 μM), its efficacy against HCT116 cancer cells was approximately 4-fold higher than that of quillaic acid. Compound E also induces cell cycle arrest and apoptosis by modulating NF-κB and MAPK pathways. Therefore, the development of compound E is certainly valuable for anti-tumor applications.

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Section: Resultsmentioning

confidence: 99%

Synthesis and evaluation of anticancer activity of quillaic acid derivatives: A cell cycle arrest and apoptosis inducer through NF-κB and MAPK pathways

et al. 2022

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“…In 2019, Huang et al 44 reported the synthesis of a series of novel steroidal β-triazolyl enones using the CuAAC click reaction and Claisen-Schmidt condensation reaction as the key steps. These new derivatives were further evaluated for their antiproliferative activity.…”

Section: Scheme 8 Synthesis Of Derivatives 24a and 24bmentioning

confidence: 99%

Recent syntheses of steroid derivatives using the CuAAC “click” reaction

Ibrahim‐Ouali¹,

Dumur²

2021

Arkivoc

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The introduction of heterocycles into steroids is often at the origin of a modification of their physiological activity and thus allows the formation of new biologically interesting molecules. Recent advances in the field of steroid synthesis using the copper-catalyzed azide-alkyne cycloaddition (CuAAC) are presented here. Compounds exhibiting known biological activities are also reported in this review. This approach holds great promise and allows us to consider preparing new, highly functionalized complex molecules using the CuAAC "click" reaction.

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“…During the development of new inhibitors of CYP17A1, a large number of androstane and pregnane derivatives have been introduced containing pyridyl-, picolidine-, pyrazolyl-, imidazolyl-, triazolyl-, isoxazolinyl-, dihydrooxazolinyl-, tetrahydrooxazolinyl-, benzimidazolyl-, and carbamoyl- substituents, mainly in positions 16, 17, and 22 [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. Galeterone, the most advanced among them and having a multiple mechanism of action, has reached phase III clinical trials [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of New Isoxazolyl Steroids as Anti-Prostate Cancer Agents

Rudovich

Peřina

Krech

et al. 2022

IJMS

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Steroids with a nitrogen-containing heterocycle in the side chain are known as effective inhibitors of androgen signaling and/or testosterone biosynthesis, thus showing beneficial effects for the treatment of prostate cancer. In this work, a series of 3β-hydroxy-5-ene steroids, containing an isoxazole fragment in their side chain, was synthesized. The key steps included the preparation of Weinreb amide, its conversion to acetylenic ketones, and the 1,2- or 1,4-addition of hydroxylamine, depending on the solvent used. The biological activity of the obtained compounds was studied in a number of tests, including their effects on 17α-hydroxylase and 17,20-lyase activity of human CYP17A1 and the ability of selected compounds to affect the downstream androgen receptor signaling. Three derivatives diminished the transcriptional activity of androgen receptor and displayed reasonable antiproliferative activity. The candidate compound, 24j (17R)-17-((3-(2-hydroxypropan-2-yl)isoxazol-5-yl)methyl)-androst-5-en-3β-ol, suppressed the androgen receptor signaling and decreased its protein level in two prostate cancer cell lines, LNCaP and LAPC-4. Interaction of compounds with CYP17A1 and the androgen receptor was confirmed and described by molecular docking.

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Design, synthesis and biological evaluation of new steroidal β-triazoly enones as potent antiproliferative agents

Cited by 14 publications

References 21 publications

Synthesis and evaluation of anticancer activity of quillaic acid derivatives: A cell cycle arrest and apoptosis inducer through NF-κB and MAPK pathways

Synthesis and evaluation of anticancer activity of quillaic acid derivatives: A cell cycle arrest and apoptosis inducer through NF-κB and MAPK pathways

Recent syntheses of steroid derivatives using the CuAAC “click” reaction

Synthesis and Biological Evaluation of New Isoxazolyl Steroids as Anti-Prostate Cancer Agents

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