Synthesis and in vitro activity of some epimeric 20α-hydroxy, 20-oxime and aziridine pregnene derivatives as inhibitors of human 17α-hydroxylase/c 17,20 -lyase and 5α-reductase

Ling, Y.; Li, Ji-song; Kato, Katsuya; Liu, Yang; Wang, Xin; Klus, Gregory T.; Marat, Kirk; Nnane, Ivo P.; Brodie, Angela

doi:10.1016/s0968-0896(98)00110-2

Cited by 31 publications

(17 citation statements)

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“…iC 50 parameters of references ketoconazole and abiraterone were found 1.86 ± 0.25 μM and 0.034 ± 0.003 µM for 17α-hydroxylase, and 0.32 ± 0.02 µM and 0.0125 ± 0.0015 µM for C 17,20 -lyase in our P450 17α inhibition test, respectively. these reference results are in good agreement with values found in the literature [4,9,15,18,23,[31][32]34]. Table 1 In vitro inhibition of 17α-hydroxylase and C 17,20 -lyase activities of the rat testicular P450 …”

Section: Methodological Investigationssupporting

confidence: 89%

“…Other versions of the radiosubstrate method use specifically labelled substrates. Hydroxylation of the [17α-3 h]Prog eliminates a tritiated water molecule [30,39], whereas cleavage of labelled C-17 side chain of 17oh-Prog produce labelled acetic acid [19,23,24,28,30]. in these techniques, enzyme activities, can be detected via measurement of labelled water or acetic acid which remains in the incubate water phase following an organic extraction.…”

Section: Discussionmentioning

confidence: 99%

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Determination of 17α-hydroxylase-C_17,20-lyase (P450_17α) enzyme activities and their inhibition by selected steroidal picolyl and picolinylidene compounds

Szabó

Ajduković

Djurendić

et al. 2015

Acta Biologica Hungarica

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17α-hydroxylase-C 17,20 -lyase (P450 17α ) is a key regulator enzyme of the steroid hormone biosynthesis in both the adrenals and the testes. inhibition of this enzyme can block androgen synthesis in an early step, and may thereby be useful in the treatment of several androgen-dependent diseases. We developed radiosubstrate in vitro incubation methods for the determination of the distinct 17α-hydroxylase and C 17,20 -lyase activities of the enzyme using rat testicular homogenate as enzyme source. With this method we have studied the inhibiting activity of selected steroidal picolyl and picolinylidene compounds. tests revealed a substantial inhibitory action of the 17-picolinyliden-androst-4-en-3-one compound.

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Section: Methodological Investigationssupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Determination of 17α-hydroxylase-C_17,20-lyase (P450_17α) enzyme activities and their inhibition by selected steroidal picolyl and picolinylidene compounds

Szabó

Ajduković

Djurendić

et al. 2015

Acta Biologica Hungarica

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“…Furthermore, steroidal epoxy compounds have been used as important intermediates to synthesize potent inhibitors of 5AR, since their facile ring opening allows the introduction of various functionalities in a stereospecific manner. Also, it was reported that the 5AR inhibitory activity was tightly dependent on the presence, position, and number of unsaturations on the A-C rings of steroid skeleton [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and 5α-Reductase Inhibitory Activity of C21 Steroids Having 1,4-diene or 4,6-diene 20-ones and 4-Azasteroid 20-Oximes

2011

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PurposeA connectome is a comprehensive description of synaptic connectivity for a neural domain. Our goal was to produce a connectome data set for the inner plexiform layer of the mammalian retina. This paper describes our first retinal connectome, validates the method, and provides key initial findings.MethodsWe acquired and assembled a 16.5 terabyte connectome data set RC1 for the rabbit retina at ≈2 nm resolution using automated transmission electron microscope imaging, automated mosaicking, and automated volume registration. RC1 represents a column of tissue 0.25 mm in diameter, spanning the inner nuclear, inner plexiform, and ganglion cell layers. To enhance ultrastructural tracing, we included molecular markers for 4-aminobutyrate (GABA), glutamate, glycine, taurine, glutamine, and the in vivo activity marker, 1-amino-4-guanidobutane. This enabled us to distinguish GABAergic and glycinergic amacrine cells; to identify ON bipolar cells coupled to glycinergic cells; and to discriminate different kinds of bipolar, amacrine, and ganglion cells based on their molecular signatures and activity. The data set was explored and annotated with Viking, our multiuser navigation tool. Annotations were exported to additional applications to render cells, visualize network graphs, and query the database.ResultsExploration of RC1 showed that the 2 nm resolution readily recapitulated well known connections and revealed several new features of retinal organization: (1) The well known AII amacrine cell pathway displayed more complexity than previously reported, with no less than 17 distinct signaling modes, including ribbon synapse inputs from OFF bipolar cells, wide-field ON cone bipolar cells and rod bipolar cells, and extensive input from cone-pathway amacrine cells. (2) The axons of most cone bipolar cells formed a distinct signal integration compartment, with ON cone bipolar cell axonal synapses targeting diverse cell types. Both ON and OFF bipolar cells receive axonal veto synapses. (3) Chains of conventional synapses were very common, with intercalated glycinergic-GABAergic chains and very long chains associated with starburst amacrine cells. Glycinergic amacrine cells clearly play a major role in ON-OFF crossover inhibition. (4) Molecular and excitation mapping clearly segregates ultrastructurally defined bipolar cell groups into different response clusters. (5) Finally, low-resolution electron or optical imaging cannot reliably map synaptic connections by process geometry, as adjacency without synaptic contact is abundant in the retina. Only direct visualization of synapses and gap junctions suffices.ConclusionsConnectome assembly and analysis using conventional transmission electron microscopy is now practical for network discovery. Our surveys of volume RC1 demonstrate that previously studied systems such as the AII amacrine cell network involve more network motifs than previously known. The AII network, primarily considered a scotopic pathway, clearly derives ribbon synapse input from photopic ON and OFF cone bipol...

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“…16-DHP is an efficient inhibitor of 17α-hydroxylase and 15α-reductase [3] . A patent declared that 16-DHP could significantly decrease blood lipid in healthy volunteers or patients with hyperlipidemia [4] .…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic behavior of 16-dehydropregnenolone after intramuscular administration in rats

Yang

Zhang

Yang

et al. 2011

Journal of Pharmaceutical Analysis

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The pharmacokinetics of 16-dehydropregnenolone (16-DHP), a sterols compound isolated from Solanum lyratum Thunb., was investigated in rats following a Single intramuscular administration (40 mg/kg). The concentration of 16-DHP in rat plasma was determined by a high Performance liquid chromatography (HPLC) method with UV detection. Levonorgestrel was used as the internal Standard (IS). The pharmacokinetic parameters of 16-DHP were derived by non-compartmental method. After a Single intramuscular administration, the maximum plasma concentration (Cmax) was (289 ± 25) ng/mL, time to reach Cmax(tmax) was (0.38 ± 0.14) h, the elimination half-life (t1/2) was (2.5 ± 1.1) h, the area under the plasma concentration-time curve from time zero to the time of the last measurable concentration (AUC(0-t)) was (544 ± 73)ng · h/mL. The results indicated that 16-DHP was absorbed quickly and eliminated rapidly in rats after the intramuscular injection.

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Synthesis and in vitro activity of some epimeric 20α-hydroxy, 20-oxime and aziridine pregnene derivatives as inhibitors of human 17α-hydroxylase/c 17,20 -lyase and 5α-reductase

Cited by 31 publications

References 31 publications

Determination of 17α-hydroxylase-C_17,20-lyase (P450_17α) enzyme activities and their inhibition by selected steroidal picolyl and picolinylidene compounds

Determination of 17α-hydroxylase-C_17,20-lyase (P450_17α) enzyme activities and their inhibition by selected steroidal picolyl and picolinylidene compounds

Synthesis and 5α-Reductase Inhibitory Activity of C21 Steroids Having 1,4-diene or 4,6-diene 20-ones and 4-Azasteroid 20-Oximes

Pharmacokinetic behavior of 16-dehydropregnenolone after intramuscular administration in rats

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Synthesis and in vitro activity of some epimeric 20α-hydroxy, 20-oxime and aziridine pregnene derivatives as inhibitors of human 17α-hydroxylase/c 17,20 -lyase and 5α-reductase

Cited by 31 publications

References 31 publications

Determination of 17α-hydroxylase-C17,20-lyase (P45017α) enzyme activities and their inhibition by selected steroidal picolyl and picolinylidene compounds

Determination of 17α-hydroxylase-C17,20-lyase (P45017α) enzyme activities and their inhibition by selected steroidal picolyl and picolinylidene compounds

Synthesis and 5α-Reductase Inhibitory Activity of C21 Steroids Having 1,4-diene or 4,6-diene 20-ones and 4-Azasteroid 20-Oximes

Pharmacokinetic behavior of 16-dehydropregnenolone after intramuscular administration in rats

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Determination of 17α-hydroxylase-C_17,20-lyase (P450_17α) enzyme activities and their inhibition by selected steroidal picolyl and picolinylidene compounds

Determination of 17α-hydroxylase-C_17,20-lyase (P450_17α) enzyme activities and their inhibition by selected steroidal picolyl and picolinylidene compounds