ChemInform Abstract: MECHANISM-BASED INACTIVATION OF CYTOCHROME P-450 BY HETEROATOM-SUBSTITUTED CYCLOPROPANES AND FORMATION OF RING-OPENED PRODUCTS

Unlike a variety of other animal species, such as the rabbit, mouse or rat, the guinea pig has a relatively long gestation period and is a more fully developed animal at birth. Kuenzig et al. reported that drug metabolic activity which increases very slowly during fetal life, increases rapidly after birth. Hepatocytes of a 3-day old neonate metabolize drugs and reduce cytochrome P-450 at a rate comparable to that observed in the adult animal. Moreover the administration of drugs like phenobarbital to pregnant guinea pigs increases the microsomal mixed function oxidase activity already in the fetus.Drug metabolic activity is, generally, localized within the smooth endoplasmic reticulum (SER) of the hepatocyte.

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Pharmacogénétique et variabilité inter individuelle de la réponse aux traitements : l’exemple du Cytochrome P-450 2C9 et des anticoagulants coumariniques.

Bulletin de l Académie Nationale de Médecine ◽

10.1016/s0001-4079(19)33352-7 ◽

2006 ◽

Vol 190 (1) ◽

pp. 37-53 ◽

Cited By ~ 2

Author(s):

Laurent Becquemont ◽

Céline Verstuyft ◽

Patrice Jaillon

Keyword(s):

Cytochrome P 450

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The Potential Role of the Cytochrome P-450 2D6 Pharmacogenetic Polymorphism in Drug Abuse

PsycEXTRA Dataset ◽

10.1037/e495572006-003 ◽

1997 ◽

Cited By ~ 1

Author(s):

Edward M. Sellers ◽

S. Victoria Otton ◽

Rachel F. Tyndale

Keyword(s):

Drug Abuse ◽

Potential Role ◽

Cytochrome P 450

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Polymorphism of p-450 cytochrome detoxication genes in adolescents depending on the degree of contamination of the organism by heavy metals

Hygiene and Sanitation ◽

10.33029/0016-9900-2020-99-5-478-482 ◽

2020 ◽

Vol 99 (5) ◽

pp. 478-482

Author(s):

N. P. Setko ◽

A. G. Setko ◽

Ekaterina V. Bulycheva ◽

A. V. Tyurin ◽

E. Yu. Kalinina

Keyword(s):

Heavy Metals ◽

Environmental Factors ◽

Heavy Metal Contamination ◽

Atomic Absorption Spectrophotometry ◽

The Body ◽

Lead And Cadmium ◽

Cyp2b6 Gene ◽

Cytochrome P 450 ◽

Gene Cyp1a1 ◽

Group 1

Introduction. Changes in the body of children and adolescents aimed at adapting to environmental factors are determined by genetic polymorphism in xenobiotic biotransformation genes, determining the degree of susceptibility of the child’s body to pollutants, which is the basis of modern personalized preventive medicine when managing risks to the health of the child population under the influence of environmental factors. Material and methods. Trace elements, including heavy metals, lead and cadmium, were determined in the hair of 256 practically healthy teenagers by atomic absorption spectrophotometry. Depending on the level of content of the latter, two groups of adolescents were formed to determine six genes of the cytochrome P-450 family. Group 1 consisted of adolescents whose cadmium lead content exceeded the average Russian indices. The second group included adolescents whose heavy metals were above the level of average Russian standards. Results. Studies have shown that in adolescents of the 1st group, compared with the data of adolescents of the 2nd group, an increase in the number of carriers of two mutant alleles at the locus rs 1048943 (gene CYP1A1) is 3.08 times, rs 464621 (gene CYP1A1) is 1. 8 times; locus rs 2069522 (CYP1A2 gene) 3.63 times; locus rs 1799853 (CYP2C9 * 2 gene) 4.5 times; locus rs 1057910 (gene CYP2C9 * 3) 3.8 times and locus rs 2279343 (gene CYP2B6) 4.25 times. Moreover, carriers of two normal alleles in adolescents of the first group at the locus rs 1048943 (gene CYP1A1) were 5.14 times; locus rs 2279343 (CYP2B6 gene) was 6.5 fold less than among adolescents of the 2nd group; and at the locus rs 464621 (gene CYP1A1), rs 2069522 (gene CYP1A2), rs 1799853 (gene CYP2C9 * 2), rs 1057910 (gene CYP2C9 * 3) there were no carriers of normal homozygotes. Conclusion. Group 1 adolescents with heavy metal contamination of the body are carriers significantly in a greater number of pathological mutations in the genes of the cytochrome P-450 detoxification system in comparison with data from group 2 adolescents.

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Oxygenation of 18-hydroxycorticosterone as the final reaction for aldosterone biosynthesis

Acta Endocrinologica ◽

10.1530/acta.0.1070395 ◽

1984 ◽

Vol 107 (3) ◽

pp. 395-400 ◽

Cited By ~ 9

Author(s):

Itaru Kojima ◽

Etsuro Ogata ◽

Hiroshi Inano ◽

Bun-ichi Tamaoki

Keyword(s):

Carbon Monoxide ◽

Hydroxysteroid Dehydrogenase ◽

Dependent Manner ◽

In Vitro Production ◽

Mitochondrial Preparation ◽

Final Reaction ◽

Vitro Production ◽

Dose Dependent ◽

Cytochrome P 450

Abstract. Incubation of 18-hydroxycorticosterone with the sonicated mitochondrial preparation of bovine adrenal glomerulosa tissue leads to the production of aldosterone, as measured by radioimmunoassay. The in vitro production of aldosterone from 18-hydroxycorticosterone requires both molecular oxygen and NADPH, and is inhibited by carbon monoxide. Cytochrome P-450 inhibitors such as metyrapone, SU 8000. SU 10603, SKF 525A, amphenone B and spironolactone decrease the biosynthesis of aldosterone from 18-hydroxycorticosterone. These results support the conclusion that the final reaction in aldosterone synthesis from 18-hydroxycorticosterone is catalyzed by an oxygenase, but not by 18-hydroxysteroid dehydrogenase. By the same preparation, the production of [3H]aldosterone but not [3H]18-hydroxycorticosterone from [1,2-3H ]corticosterone is decreased in a dose-dependent manner by addition of non-radioactive 18-hydroxycorticosterone.

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Three-Component [1+1+1] Cyclopropanation with Ruthenium(II)

10.26434/chemrxiv.6025772 ◽

2018 ◽

Author(s):

Tanner C. Jankins ◽

Robert R. Fayzullin ◽

Eugene Khaskin

Keyword(s):

Quaternary Carbon ◽

Poor Control ◽

One Step ◽

Synthetic Routes ◽

Mechanistic Investigations ◽

Chiral Centers ◽

Metal Catalyzed ◽

The Right ◽

Substituted Cyclopropanes

We report a one-step, Ru(II)-catalyzed cyclopropanation reaction that is conceptually different from the previously reported protocols that include Corey-Chaykovsky, Simmons-Smith, and metal catalyzed carbene attack on olefins. Under the current protocol, various alcohols are transformed into sulfone substituted cyclopropanes with excellent isolated yields and diastereoselectivities. This new reaction forms highly congested cyclopropane products with three new C–C bonds, three or two new chiral centers and one new quaternary carbon center. 22 examples of isolated substrates are given. Previously reported synthetic routes for similar substrates are all multi-step, linear routes that proceed with overall low yields and poor control of stereochemistry. Experimental mechanistic investigations suggest initial metal-catalyzed dehydrogenation of the alcohol substrate and catalyst independent stepwise attack of two equivalents of sulfone on the aldehyde under basic conditions. While the Ru(II) is only responsible for the initial dehydrogenation step, the rate of aldehyde formation is crucial to maintaining the right balance of intermediates needed to afford the cyclopropane product.

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Enantioselective Multi-Component Cyclopropane Synthesis Enabled by Cu-Catalyzed Cyclopropene Carbometallation with Organoboron Reagent

10.26434/chemrxiv.7011548 ◽

2018 ◽

Author(s):

Zhanyu Li ◽

Mengru Zhang ◽

Yu Zhang ◽

Shuang Liu ◽

Jinbo Zhao ◽

...

Keyword(s):

Carbon Source ◽

Stereoselective Synthesis ◽

Organometallic Reagents ◽

Preliminary Results ◽

Quaternary Center ◽

Chiral Centers ◽

Substituted Cyclopropanes ◽

Proof Of Principle

Deployment of organoboron in lieu of the strongly basic organometallic reagents as carbon source in Cu-catalyzed cyclopropene carbometallation opens unprecedented three- component reactivity for stereoselective synthesis of poly-substituted cyclopropanes. A proof-of-principle demonstration of this novel carbometallation strategy is presented herein for a highly convergent access to poly-substituted aminocyclopropane framework via carboamination. Preliminary results on asymmetric desymmetrization with commercial bisphosphine ligands attained high levels of enantioselection, offering a straightforward access to enantioenriched aminocyclopropanes bearing all-three chiral centers, including an all-carbon quaternary center. This strategy may underpin a host of novel synthetic protocols for poly-substituted cyclopropanes.

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