0000000000786468

AUTHOR

Olli Kärkkäinen

showing 4 related works from this author

Molecular docking and oxidation kinetics of 3-phenyl coumarin derivatives by human CYP2A13.

2021

CYP2A13 enzyme is expressed in human extrahepatic tissues, while CYP2A6 is a hepatic enzyme. Reactions catalysed by CYP2A13 activate tobacco-specific nitrosamines and some other toxic xenobiotics in lungs.To compare oxidation characteristics and substrate-enzyme active site interactions in CYP2A13 vs CYP2A6, we evaluated CYP2A13 mediated oxidation characteristics of 23 coumarin derivatives and modelled their interactions at the enzyme active site.CYP2A13 did not oxidise six coumarin derivatives to corresponding fluorescent 7-hydroxycoumarins. The Km-values of the other coumarins varied 0.85-97 µM, Vmax-values of the oxidation reaction varied 0.25-60 min-1, and intrinsic clearance varied 26-…

Health Toxicology and MutagenesisKineticsToxicology030226 pharmacology & pharmacyBiochemistryRedoxMedicinal chemistryCytochrome P-450 CYP2A603 medical and health scienceschemistry.chemical_compound0302 clinical medicineCytochrome P-450 Enzyme SystemCoumarinsHumansheterocyclic compoundsEnzyme kineticsCYP2A6Pharmacologychemistry.chemical_classificationbiologyChemistryActive siteGeneral MedicineCoumarinMolecular Docking SimulationKineticsEnzymeDocking (molecular)030220 oncology & carcinogenesisbiology.proteinAryl Hydrocarbon HydroxylasesXenobiotica; the fate of foreign compounds in biological systems
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In vitro sulfonation of 7-hydroxycoumarin derivatives in liver cytosol of human and six animal species

2020

Sulfonation is an important high affinity elimination pathway for phenolic compounds.In this study sulfonation of 7-hydroxycoumarin and 13 its derivatives were evaluated in liver cytosols of human and six animal species. 7-hydroxycoumarin and its derivatives are strongly fluorescent, and their sulfate conjugates are nonfluorescent at excitation 405 nm and emission 460 nm. A convenient fluorescence based kinetic assay of sulfonation was established.The sulfonation rate of most of the 7-hydroxycoumarin derivatives was low in liver cytosol of human and pig, whereas it was high with most compounds in dog and intermediate in rat, mouse, rabbit, and sheep. Sulfonation of the 7-hydroxycoumarin der…

Health Toxicology and MutagenesisLiver cytosolToxicologyliver030226 pharmacology & pharmacyBiochemistryArticle03 medical and health sciences0302 clinical medicineanimalhumanAnimal specieskumariinitsulfonationPharmacologyChemistrymaksaGeneral MedicinelääkeaineetIn vitroBiochemistry7-hydroxycoumarinfarmakokinetiikka030220 oncology & carcinogenesiseläimetihmiset
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In vitro glucuronidation of 7-hydroxycoumarin derivatives in intestine and liver microsomes of Beagle dogs

2019

Beagle dog is a standard animal model for evaluating nonclinical pharmacokinetics of new drug candidates. Glucuronidation in intestine and liver is an important first-pass drug metabolic pathway, especially for phenolic compounds. This study evaluated the glucuronidation characteristics of several 7-hydroxycoumarin derivatives in beagle dog's intestine and liver in vitro. To this end, glucuronidation rates of 7-hydroxycoumarin (compound 1), 7-hydroxy-4-trifluoromethylcoumarin (2), 6-methoxy-7-hydroxycoumarin (3), 7-hydroxy-3-(4-tolyl)coumarin (4), 3-(4-fluorophenyl)coumarin (5), 7-hydroxy-3-(4-hydroxyphenyl)coumarin (6), 7-hydroxy-3-(4-methoxyphenyl)coumarin (7), and 7-hydroxy-3-(1H-1,2,4-t…

entsyymitColonGlucuronidationPharmaceutical Science02 engineering and technologyliver030226 pharmacology & pharmacyBeaglekoira7-hydroxycoumarin derivative03 medical and health scienceschemistry.chemical_compound0302 clinical medicineDogsGlucuronidesPharmacokineticsMicrosomesenzyme kineticsIntestine SmallmedicineAnimalsHumansUmbelliferonesGlucuronosyltransferasekumariinitaineenvaihduntachemistry.chemical_classificationChemistryglucuronidationdog intestinemaksaMetabolismlääkeaineet021001 nanoscience & nanotechnologyCoumarinSmall intestineEnzymemedicine.anatomical_structureBiochemistryLiverfarmakokinetiikkasuolistoMicrosomekoe-eläinmallit0210 nano-technology
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Molecular docking and oxidation kinetics of 3-phenyl coumarin derivatives by human CYP2A13

2021

CYP2A13 enzyme is expressed in human extrahepatic tissues, while CYP2A6 is a hepatic enzyme. Reactions catalysed by CYP2A13 activate tobacco-specific nitrosamines and some other toxic xenobiotics in lungs.To compare oxidation characteristics and substrate-enzyme active site interactions in CYP2A13 vs CYP2A6, we evaluated CYP2A13 mediated oxidation characteristics of 23 coumarin derivatives and modelled their interactions at the enzyme active site.CYP2A13 did not oxidise six coumarin derivatives to corresponding fluorescent 7-hydroxycoumarins. The Km-values of the other coumarins varied 0.85���97 ��M, Vmax-values of the oxidation reaction varied 0.25���60 min���1, and intrinsic clearance var…

entsyymitCYP2A13biokemiaoxidationenzyme kineticsmolekyylidynamiikkaheterocyclic compoundsin silico -menetelmä3-phenyl coumarinhapetus-pelkistysreaktiokumariinitin silico modeling
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