Genomes and Genes
Summary: The removing of alkyl groups from a compound. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)
- Chang T, Yeung R. Effect of trans-resveratrol on 7-benzyloxy-4-trifluoromethylcoumarin O-dealkylation catalyzed by human recombinant CYP3A4 and CYP3A5. Can J Physiol Pharmacol. 2001;79:220-6 pubmed..Trans-resveratrol inhibited BFC O-dealkylation catalyzed by CYP3A4 and CYP3A5 in a concentration-dependent manner...
- Liu H, Llano J, Gauld J. A DFT study of nucleobase dealkylation by the DNA repair enzyme AlkB. J Phys Chem B. 2009;113:4887-98 pubmed publisherOxidative dealkylation is a unique mechanistic pathway found in the alpha-ketoglutarate-Fe(II)-dependent AlkB family of enzymes to remove the alkylation damage to DNA bases and regenerate nucleobases to their native state...
- Caccia S. N-dealkylation of arylpiperazine derivatives: disposition and metabolism of the 1-aryl-piperazines formed. Curr Drug Metab. 2007;8:612-22 pubmed..Most of them undergo extensive pre-systemic and systemic metabolism including CYP3A4-dependent N-dealkylation to 1-aryl-piperazines...
- Upthagrove A, Nelson W. Carbinolamines, imines, and oxazolidines from fluorinated propranolol analogs. (19)F NMR and mass spectral characterization and evidence for formation as intermediates in cytochrome P450-catalyzed N-dealkylation. Drug Metab Dispos. 2001;29:1114-22 pubmed..trap conditions showed formation of imine metabolites (and/or oxazolidine from 7) as well as products of N-dealkylation and aromatic hydroxylation when the secondary amine substrates were incubated with rat liver microsomes or ..
- Ward B, Morocho A, Kandil A, Galinsky R, Flockhart D, Desta Z. Characterization of human cytochrome P450 enzymes catalyzing domperidone N-dealkylation and hydroxylation in vitro. Br J Clin Pharmacol. 2004;58:277-87 pubmed..In HLMs, domperidone underwent hydroxylation to form 5-hydroxydomperidone (MIII) and N-dealkylation to form 2,3-dihydro-2-oxo-1H-benzimidazole-1-propionic acid (MI) and 5-chloro-4-piperidinyl-1,3-dihydro-..
- Fang D, Lord R, Cisneros G. Ab initio QM/MM calculations show an intersystem crossing in the hydrogen abstraction step in dealkylation catalyzed by AlkB. J Phys Chem B. 2013;117:6410-20 pubmed publisherAlkB is a bacterial enzyme that catalyzes the dealkylation of alkylated DNA bases. The rate-limiting step is known to be the abstraction of an H atom from the alkyl group on the damaged base by a Fe(IV)-oxo species in the active site...
- Hynninen V, Olkkola K, Bertilsson L, Kurkinen K, Neuvonen P, Laine K. Effect of terbinafine and voriconazole on the pharmacokinetics of the antidepressant venlafaxine. Clin Pharmacol Ther. 2008;83:342-8 pubmed
- Marquardt S, Raitskin O, Wu Z, Liu F, Sun Q, Dean C. Functional consequences of splicing of the antisense transcript COOLAIR on FLC transcription. Mol Cell. 2014;54:156-165 pubmed publisher..Our findings suggest that altered splicing of a long noncoding transcript can quantitatively modulate gene expression through cotranscriptional coupling mechanisms...
- Castella M, Reist M, Mayer J, Turban J, Testa B, Boursier Neyret C, et al. Development of an in vitro rat intestine segmental perfusion model to investigate permeability and predict oral fraction absorbed. Pharm Res. 2006;23:1543-53 pubmed..Up to six permeation kinetics can be obtained per rat, and the method has shown to be a valuable tool to estimate human oral absorption. ..
- Mandl J, Szarka A, Banhegyi G. Vitamin C: update on physiology and pharmacology. Br J Pharmacol. 2009;157:1097-110 pubmed publisher..Recently discovered functions of ascorbate in nucleic acid and histone dealkylation and proteoglycan deglycanation are also summarized...
- Pazos Y, Iglesias B, de Lera A. The Suzuki coupling reaction in the stereocontrolled synthesis of 9-cis-retinoic acid and its ring-demethylated analogues. J Org Chem. 2001;66:8483-9 pubmed..Both Suzuki and Stille coupling reactions took place under mild conditions, and the preservation of the retinoid side-chain geometry was therefore secured. ..
- Loos R, Niessner R. Analysis of atrazine, terbutylazine and their N-dealkylated chloro and hydroxy metabolites by solid-phase extraction and gas chromatography-mass spectrometry and capillary electrophoresis-ultraviolet detection. J Chromatogr A. 1999;835:217-29 pubmed..6 or a sodium borate-sodium dodecyl sulfate buffer at pH 9.3. The combined method of SPE enrichment and CE analysis allows the determination of HTDPs in the low microgram/l range. ..
- Nagahori H, Saito K, Tomigahara Y, Isobe N, Kaneko H. Metabolism of pyridalyl in rats. Drug Metab Dispos. 2009;37:2284-9 pubmed publisher..7 to 2.6 and 98.7 to 101.7%, respectively. One urinary and fecal major metabolite (resulting from O-dealkylation) and two minor metabolites were identified by NMR and mass spectrometry...
- de Bruijn P, Sleijfer S, Lam M, Mathijssen R, Wiemer E, Loos W. Bioanalytical method for the quantification of sunitinib and its n-desethyl metabolite SU12662 in human plasma by ultra performance liquid chromatography/tandem triple-quadrupole mass spectrometry. J Pharm Biomed Anal. 2010;51:934-41 pubmed publisher..200 to 50.0ng/ml with the lower limit of quantitation validated at 0.200ng/ml for both sunitinib and SU12662. The within-run and between-run precisions were within 11.7%, while the accuracy ranged from 90.5 to 106.8%. ..
- Gu Y, Atwell G, Wilson W. Metabolism and excretion of the novel bioreductive prodrug PR-104 in mice, rats, dogs, and humans. Drug Metab Dispos. 2010;38:498-508 pubmed publisher..The major urinary metabolites in mice were products from oxidative N-dealkylation and/or glutathione conjugation of the nitrogen mustard moiety, including subsequent mercapturic acid pathway ..
- Porrogi P, Kóbori L, Kohalmy K, Gulyás J, Vereczkey L, Monostory K. Limited applicability of 7-methoxy-4-trifluoromethylcoumarin as a CYP2C9-selective substrate. Pharmacol Rep. 2008;60:972-9 pubmed..support the participation of several P450 enzymes (CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2E1 and CYP3A4) in MFC O-dealkylation. Therefore, MFC cannot be considered a suitable probe substrate in models that express several P450s, such as ..
- Masson P, Nachon F, Lockridge O. Structural approach to the aging of phosphylated cholinesterases. Chem Biol Interact. 2010;187:157-62 pubmed publisher..This process, termed "aging", results from dealkylation of the adduct and depends on the structure of the organophosphyl moiety...
- Pan Y, Abd Rashid B, Ismail Z, Ismail R, Mak J, Pook P, et al. In vitro modulatory effects on three major human cytochrome P450 enzymes by multiple active constituents and extracts of Centella asiatica. J Ethnopharmacol. 2010;130:275-83 pubmed publisher..This study suggested that CA could cause drug-herb interactions through CYP2C9 inhibition. ..
- Dávila Borja V, Belmont J, Espinosa J, Moreno Sanchez R, Albores A, Montero R. Induction of CYP1A1 and CYP2E1 in rat liver by histamine: binding and kinetic studies. Arch Toxicol. 2007;81:697-709 pubmed..Activity measurements using the O-dealkylation of ethoxyresorufin indicated that HA is a mixed-type inhibitor of CYP1A1 in both microsomes and supersomes...
- Wu W, McKown L, Kuo G. Hepatic metabolism of two alpha-1A-adrenergic receptor antagonists, phthalimide-phenylpiperazine analogs (RWJ-69205 and RWJ-69471), in the rat, dog and human. Eur J Drug Metab Pharmacokinet. 2006;31:271-6 pubmed..phenylhydroxylation, 2. O-dealkylation, 3. oxidative N-dealkylation, 4. N-dephenylation, and 5. dehydration...
- Dowty M, Hu G, Hua F, Shilliday F, Dowty H. Drug design structural alert: formation of trifluoroacetaldehyde through N-dealkylation is linked to testicular lesions in rat. Int J Toxicol. 2011;30:546-50 pubmed publisher..illustrates how using trifluoroethane as a part of a novel chemical entity led to cytochrome P450 - mediated N-dealkylation and the formation of trifluoroacetaldehyde, a known testicular toxicant, in exploratory safety studies in rats...
- Kirchheiner J, Schmidt H, Tzvetkov M, Keulen J, Lotsch J, Roots I, et al. Pharmacokinetics of codeine and its metabolite morphine in ultra-rapid metabolizers due to CYP2D6 duplication. Pharmacogenomics J. 2007;7:257-65 pubmed..It might be good if physicians would know about the CYP2D6 duplication genotype of their patients before administering codeine. ..
- Meyer M, Lindauer C, Maurer H. Dimethocaine, a synthetic cocaine derivative: studies on its in vitro metabolism catalyzed by P450s and NAT2. Toxicol Lett. 2014;225:139-46 pubmed publisher..However, a slow acetylation phenotype or inhibition of NAT2 could lead to decreased N-acetylation and hence leading to an increased risk of side effects caused by this arylamine. ..
- Pusalkar S, Plesescu M, Milton M, Balani S, Chowdhury S, Prakash S. Metabolism, Excretion and Pharmacokinetics of MLN3897, a CCR1 Antagonist, in Humans. Drug Metab Lett. 2016;10:22-37 pubmed..N-oxidation of the tricyclic moiety (M28) and N-dealkylation of the piperidinyl moiety were the primary metabolic pathways leading to further formation of the carboxylic ..
- Maier H, Ostraat R, Gao H, Fields S, Shinton S, Medina K, et al. Early B cell factor cooperates with Runx1 and mediates epigenetic changes associated with mb-1 transcription. Nat Immunol. 2004;5:1069-77 pubmed..EBF function was enhanced by interaction with the transcription factor Runx1. These data suggest a molecular basis for the hierarchical dependence of Pax5 function on EBF and E2A in B lymphocyte development. ..
- Ripper J, Tiekink E, Scammells P. Photochemical N-demethylation of alkaloids. Bioorg Med Chem Lett. 2001;11:443-5 pubmed..Dextromethorphan also underwent a N-demethylation reaction, but reacted further to afford an imine. In contrast, 14-acyloxycodeinones underwent a photochemically induced tandem N-demethylation acyl migration. ..
- Staack R, Theobald D, Paul L, Springer D, Kraemer T, Maurer H. In vivo metabolism of the new designer drug 1-(4-methoxyphenyl)piperazine (MeOPP) in rat and identification of the human cytochrome P450 enzymes responsible for the major metabolic step. Xenobiotica. 2004;34:179-92 pubmed..6. O-demethylation was significantly lower in PM HLM compared with pHLM (70.6% +/- 7.2%). 7. These data suggest that polymorphically expressed CYP2D6 is the enzyme mainly responsible for MeOPP O-demethylation. ..
- Suzuki Y, Ojika M, Sakagami Y. Biotransformation of cystothiazole A, a myxobacterial antibiotic, into novel derivatives by the mother producer, Cystobacter fuscus. Biosci Biotechnol Biochem. 2004;68:390-6 pubmed..Based on the time-dependent production profile and chemical structures of these derivatives, pathways for the conversion of cystothiazole A to the more polar derivatives of this antibiotic by C. fuscus are proposed. ..
- Nebbia C, Ceppa L, Dacasto M, Carletti M, Nachtmann C. Oxidative metabolism of monensin in rat liver microsomes and interactions with tiamulin and other chemotherapeutic agents: evidence for the involvement of cytochrome P-450 3A subfamily. Drug Metab Dispos. 1999;27:1039-44 pubmed..These results suggest that P-450 3A plays an important role in the oxidative metabolism of MON and that compounds capable of binding or inhibiting this isoenzyme could be expected to give rise to toxic interactions with the ionophore. ..
- Molden E, Helen Bøe G, Christensen H, Reubsaet L. High-performance liquid chromatography-mass spectrometry analysis of diltiazem and 11 of its phase I metabolites in human plasma. J Pharm Biomed Anal. 2003;33:275-85 pubmed
- Garcia Granados A, Melguizo E, Parra A, Simeó Y, Viseras B, Dobado J, et al. Regioselective enzymatic acylations of polyhydroxylated eudesmanes: semisynthesis, theoretical calculations, and biotransformation of cyclic sulfites. J Org Chem. 2000;65:8214-23 pubmed..While the R-sulfite gave 2 alpha- and 11 beta-hydroxylated metabolites, the S-sulfite yielded only regioselective deacetylations. Furthermore, both sulfites showed different reactivities in redox processes. ..
- Spigset O, Hagg S, Stegmayr B, Dahlqvist R. Citalopram pharmacokinetics in patients with chronic renal failure and the effect of haemodialysis. Eur J Clin Pharmacol. 2000;56:699-703 pubmed..The contribution of haemodialysis to the total elimination of citalopram is negligible. ..
- Singh I, Prasad A, Sharma A, Saxena R, Olsen C, Cholli A, et al. Synthetic and novel biocatalytic resolution studies on (+/-)-5/6/7-acetoxy-4-aryl-3,4-dihydrocoumarins. Bioorg Med Chem. 2003;11:529-38 pubmed..This is one of the rare examples of resolution using phenolic ester moiety as a remote handle for chiral recognition by a lipase. ..
- Xie L, Akao T, Hamasaki K, Deyama T, Hattori M. Biotransformation of pinoresinol diglucoside to mammalian lignans by human intestinal microflora, and isolation of Enterococcus faecalis strain PDG-1 responsible for the transformation of (+)-pinoresinol to (+)-lariciresinol. Chem Pharm Bull (Tokyo). 2003;51:508-15 pubmed..Furthermore, a bacterial strain responsible for the transformation of (+)-pinoresinol to (+)-lariciresinol was isolated from a human fecal suspension and identified as Enterococcus faecalis strain PDG-1. ..
- Dragoni S, Bellik L, Frosini M, Sgaragli G, Marini S, Gervasi P, et al. l-Deprenyl metabolism by the cytochrome P450 system in monkey (Cercopithecus aethiops) liver microsomes. Xenobiotica. 2003;33:181-95 pubmed..component than for the high K(m), suggesting that the former component is the major determinant of l-deprenyl N-dealkylation. At 15 micro M l-deprenyl, both ketoconazole and 8-methoxypsoralen significantly inhibited l-methamphetamine ..
- Issar M, Singh S, Madhusudanan K, Mishra B, Gupta R. Metabolism and excretion of centbutindole (neuroleptic) in rats after oral administration. J Pharm Pharmacol. 2002;54:1623-30 pubmed..of centbutindole include reduction of the carbonyl functional group in the butyrophenone side chain and N-dealkylation of the butyrophenone side chain attached to the pyrazinopyridoindole ring nitrogen at position 2...
- Liu Z, Chen D, Huang L, Tao Y, Yao M, Yuan Z. In vitro biotransformation and investigation of metabolic enzymes possibly responsible for the metabolism of bisdesoxyolaquindox in the liver fractions of rats, chicken, and pigs. Toxicology. 2011;279:155-66 pubmed publisher..in the three species were the oxidation of hydroxyl to bisdesoxyolaquindox-2'-carboxyl acid (O10) and the N-dealkylation of the side chain to 3-methylquinoxaline 2-carboxamide (O12)...
- Broly F, Libersa C, Lhermitte M, Dupuis B. Inhibitory studies of mexiletine and dextromethorphan oxidation in human liver microsomes. Biochem Pharmacol. 1990;39:1045-53 pubmed..These data suggest that the formation of two major metabolites of mexiletine is predominantly catalysed by the genetically variable human liver P-450dbl. ..
- Ohman D, Norlander B, Peterson C, Bengtsson F. Bioanalysis of racemic reboxetine and its desethylated metabolite in a therapeutic drug monitoring setting using solid phase extraction and HPLC. Ther Drug Monit. 2001;23:27-34 pubmed..In conclusion, these results suggest that a routine reboxetine therapeutic drug monitoring service that is robust enough to produce reliable and reproducible results may be introduced into everyday clinical practice. ..
- Locuson C, Alfaro J, Zaya M, Billen D, White J, Jones J. A non-acidic sulfaphenazole analog demonstrating high intrinsic clearance and selectivity by canine CYP2C21. Drug Metab Lett. 2011;5:253-8 pubmed..The findings suggest that canine CYP2C21, unlike human CYP2C9, does not derive ligand binding affinity from an anion binding interaction with sulfaphenazole analogs. ..
- Yamashita Y, Sumi N, Arimoto S, Hayatsu H. Synergistic action of N-nitrosodialkylamines and near-UV in the induction of chromosome aberrations in Chinese hamster lung fibroblasts in vitro. Mutat Res. 1995;348:163-8 pubmed
- Witkamp R, Nijmeijer S, Mennes W, Rozema A, Noordhoek J, Van Miert A. Regioselective O-demethylation of scoparone (6,7-dimethoxycoumarin) to assess cytochrome P450 activities in vitro in rat. Effects of gonadal steroids and the involvement of constitutive P450 enzymes. Xenobiotica. 1993;23:401-10 pubmed..This lack of selectivity limits the usefulness of scoparone as a general indicator substrate for P450 differentiation in rats. ..
- Lee H, Lee H, Choi J, Lee H. High performance liquid chromatographic analysis of a new proton pump inhibitor KR60436 and its active metabolite O-demethyl-KR60436 in rat plasma samples using column-switching. Arch Pharm Res. 2001;24:207-10 pubmed..The response was linear (r2 > or = 0.999) over the concentration range of 5-500 ng/ml. ..
- Lee D, Lippard S. Synthetic analogue of the [Fe(2)(mu-OH)(2)(mu-O(2)CR)](3+) core of soluble methane monooxygenase hydroxylase via synthesis and dioxygen reactivity of carboxylate-bridged diiron(II) complexes. Inorg Chem. 2002;41:827-37 pubmed..Compound 6 reacts with dioxygen to afford PhCHO in approximately 60(5)% yield, following oxidative N-dealkylation of the pendant benzyl group on the diamine ligand...
- Guengerich F, Miller G, Hanna I, Sato H, Martin M. Oxidation of methoxyphenethylamines by cytochrome P450 2D6. Analysis of rate-limiting steps. J Biol Chem. 2002;277:33711-9 pubmed..However, all the rates of individual steps (or rates of combined steps) are considerably higher than k(cat), and the contributions of several steps must be considered in understanding rates of the P450 2D6 reactions. ..
- Di Marco M, Edwards D, Wainer I, Ducharme M. The effect of grapefruit juice and seville orange juice on the pharmacokinetics of dextromethorphan: the role of gut CYP3A and P-glycoprotein. Life Sci. 2002;71:1149-60 pubmed..Grapefruit and seville orange juice appeared to have the same overall effect on DM pharmacokinetics. In addition, this paper presents a novel method of phenotyping for CYP2D6, CYP3A and P-glycoprotein using DM as a probe. ..
- Zhang D, He K, Raghavan N, Wang L, Mitroka J, Maxwell B, et al. Comparative metabolism of 14C-labeled apixaban in mice, rats, rabbits, dogs, and humans. Drug Metab Dispos. 2009;37:1738-48 pubmed publisher..Overall, apixaban was effectively eliminated via multiple elimination pathways in animals and humans, including oxidative metabolism, and direct renal and intestinal excretion. ..
- Arinç E, Bozcaarmutlu A. Catalyzation of cocaine N-demethylation by cytochromes P4502B, P4503A, and P4502D in fish liver. J Biochem Mol Toxicol. 2003;17:169-76 pubmed
- Laird W, Gledhill A, Lappin G. Metabolism of methyl-(E)-2-[2-[6-(2-cyanophenoxy)pyrimidin-4-yloxy]phenyl]-3-methoxyacrylate (azoxystrobin) in rat. Xenobiotica. 2003;33:677-90 pubmed..There were also several other minor pathways. ..
- Allegaert K, van Schaik R, Vermeersch S, Verbesselt R, Cossey V, Vanhole C, et al. Postmenstrual age and CYP2D6 polymorphisms determine tramadol o-demethylation in critically ill neonates and infants. Pediatr Res. 2008;63:674-9 pubmed publisher..Besides compound-specific relevance, CYP2D6 iso-enzyme specific data on in vivo ontogeny of O-demethylation can contribute to safer and more effective administration of drugs metabolized by the same route in this population. ..
- Masai E, Sasaki M, Minakawa Y, Abe T, Sonoki T, Miyauchi K, et al. A novel tetrahydrofolate-dependent O-demethylase gene is essential for growth of Sphingomonas paucimobilis SYK-6 with syringate. J Bacteriol. 2004;186:2757-65 pubmed..64:836-842, 1998). Disruption of ligH resulted in the same phenotype as DC-49; its cell extract, however, was found to be able to convert vanillate and syringate in the presence of H(4)folate. The possible role of ligH is discussed. ..
- Bonnefoy A, Dupuis Hamelin C, Steier V, Delachaume C, Seys C, Stachyra T, et al. In vitro activity of AVE1330A, an innovative broad-spectrum non-beta-lactam beta-lactamase inhibitor. J Antimicrob Chemother. 2004;54:410-7 pubmed..Only 2 mg/L were required to inhibit other Proteeae, Enterobacter, Salmonella and Serratia. The combination of ceftazidime with AVE1330A exhibited broad-spectrum activity against Ambler class A- and class C-producing Enterobacteriaceae. ..
- Blake M, Gaedigk A, Pearce R, Bomgaars L, Christensen M, Stowe C, et al. Ontogeny of dextromethorphan O- and N-demethylation in the first year of life. Clin Pharmacol Ther. 2007;81:510-6 pubmed..In contrast, DM N-demethylation developed significantly more slowly over the first year of life. Genotype and the temporal acquisition of drug biotransformation are critical determinants of a drug response in infants. ..