Discovery of a novel hybrid from finasteride and epristeride as 5α-reductase inhibitor

Yao, Zhiyi; Xu, Yan; Jiang, Sheng; Nicklaus, Marc C.; Liao, Chenzhong

doi:10.1016/j.bmcl.2010.10.112

Cited by 29 publications

(15 citation statements)

References 16 publications

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“…Among the androgens, testosterone is the most abundant in serum and secreted primarily by the testicles and ovaries. The enzyme steroid 5α-reductase catalyzes the conversion of testosterone to the most potent natural androgen, 5α-dihydrotestosterone (Yamana et al, 2010;Yao et al, 2011;Azzouni et al, 2012). Therefore, inhibition of testosterone 5α-reductase could be useful for the treatment of the above diseases.…”

Section: Effects Of the Methanol Extract From The Flowers Of M Siamementioning

confidence: 99%

Geranylated Coumarins From Thai Medicinal Plant Mammea siamensis With Testosterone 5α-Reductase Inhibitory Activity

et al. 2020

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Section: Effects Of the Methanol Extract From The Flowers Of M Siamementioning

confidence: 99%

Geranylated Coumarins From Thai Medicinal Plant Mammea siamensis With Testosterone 5α-Reductase Inhibitory Activity

et al. 2020

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“…Thus, several in silico structures of steroid 5α-reductase have recently been reported to use as a surrogate structure in the screening of potential inhibitors of this enzyme. [17][18][19] Previously, it was reported that avicequinone C (5a), a furanonaphthoquinone, isolated from the methanolic extract of Avicennia marina, could inhibit the activity of steroid 5α-reductase type 1 at a micromolar scale (IC 50 =38.8 µM). This finding was based on the use of a newly developed nonradioactive human hair dermal papilla cell-based assay, which directly detects dihydrotestosterone (DHT, 2), the enzymatic product, by high performance thin layer chromatography (HPTLC).…”

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confidence: 99%

Synthesis, Biological Evaluation and Molecular Docking of Avicequinone C Analogues as Potential Steroid 5α-Reductase Inhibitors

Karnsomwan

Netcharoensirisuk

Rungrotmongkol

et al. 2017

CHEMICAL & PHARMACEUTICAL BULLETIN

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Avicequinone C (5a), a furanonaphthoquinone isolated from the Thai mangrove Avicennia marina has been shown previously to have interesting steroid 5α-reductase type 1 inhibitory activity. In this study, a series of avicequinone C analogues containing furanonaphthoquinone with different degrees of saturation and substituents at the furan ring were synthesized. The resulting synthetic avicequinone C and analogues (5a-f) along with some related compounds including 2,5-dihydroxy-1,4-benzoquinone (6) and natural naphthoquinones such as lawsone (7a) and lapachol (7b) were evaluated for their in vitro cell viability and steroid 5α-reductase type 1 inhibitory activities using the cultured cell line of human keratinocytes (HaCaT). This cell-based bioassay was performed based on a direct detection of the enzymatic product dihydrotestosterone (2) by using a non-radioactive high performance thin layer chromatography (HPTLC) method. Among the furanonaphthoquinones in this series, 5e having a propionic substituent at furan ring possessed approximately 22-fold more potent than the original isolated compound 5a. However, the compounds without furan motif such as 6, 7a and b could not inhibit the activity of steroid 5α-reductase. Molecular docking results of the in silico three-dimensional steroid 5α-reductase type 1-reduced nicotinamide adenine dinucleotide phosphate (NADPH) binary complex was performed via AutoDock Vina and it illustrated that the furanonaphthoquinone moiety and the substituent at furan ring might play a key role as pharmacophores for the steroid 5α-reductase inhibitory activity.

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“…Functional similarities are known with 5BR (Yao et al, 2011), the structure of which is well known and present in the PDB database. Furthermore, 5AR and 5BR share the same substrate (testosterone) and inhibitor (finasteride).…”

Section: Methodsmentioning

confidence: 99%

Hypothesis onSerenoa repens(Bartram) small extract inhibition of prostatic 5α-reductase through anin silicoapproach on 5β-reductase x-ray structure

Governa

Giachetti

Biagi

et al. 2016

PeerJ

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Benign prostatic hyperplasia is a common disease in men aged over 50 years old, with an incidence increasing to more than 80% over the age of 70, that is increasingly going to attract pharmaceutical interest. Within conventional therapies, such as α-adrenoreceptor antagonists and 5α-reductase inhibitor, there is a large requirement for treatments with less adverse events on, e.g., blood pressure and sexual function: phytotherapy may be the right way to fill this need. Serenoa repens standardized extract has been widely studied and its ability to reduce lower urinary tract symptoms related to benign prostatic hyperplasia is comprehensively described in literature. An innovative investigation on the mechanism of inhibition of 5α-reductase by Serenoa repens extract active principles is proposed in this work through computational methods, performing molecular docking simulations on the crystal structure of human liver 5β-reductase. The results confirm that both sterols and fatty acids can play a role in the inhibition of the enzyme, thus, suggesting a competitive mechanism of inhibition. This work proposes a further confirmation for the rational use of herbal products in the management of benign prostatic hyperplasia, and suggests computational methods as an innovative, low cost, and non-invasive process for the study of phytocomplex activity toward proteic targets.

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Discovery of a novel hybrid from finasteride and epristeride as 5α-reductase inhibitor

Cited by 29 publications

References 16 publications

Geranylated Coumarins From Thai Medicinal Plant Mammea siamensis With Testosterone 5α-Reductase Inhibitory Activity

Geranylated Coumarins From Thai Medicinal Plant Mammea siamensis With Testosterone 5α-Reductase Inhibitory Activity

Synthesis, Biological Evaluation and Molecular Docking of Avicequinone C Analogues as Potential Steroid 5α-Reductase Inhibitors

Hypothesis onSerenoa repens(Bartram) small extract inhibition of prostatic 5α-reductase through anin silicoapproach on 5β-reductase x-ray structure

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