FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1985423401> ?p ?o ?g. }

• W1985423401 endingPage "639" @default.
• W1985423401 startingPage "633" @default.
• W1985423401 abstract "1. The aim of the present study was to investigate the structural requirements for the inhibition of 6-methyl-hydroxylation of the antitumour agent 5,6-dimethyl-xanthenone-4-acetic acid (DMXAA) by acridine analogues and use a CYP1A2 homology model to provide some insight into this interaction. 2. Concentrations causing 50% inhibition (IC50) of the 6-methylhydroxylation of DMXAA were determined in human liver microsomes in the presence of various acridines. Some of the acridines were also tested for their ability to inhibit the CYP1A2-mediated 7-ethoxyresorufin O-de-ethylation. The molecular modelling studies of human CYP1A2 used the crystal structure of rabbit CYP2C5 as a template based on protein sequence homology and an interactive docking procedure using a dynamic hydrogen bond feature. 3. The in vitro IC50 studies for the inhibition of 6-methylhydroxylation of DMXAA indicated: (i) the importance of the position of the carboxamide side-chain on the acridine nucleus (and, to a lesser extent, its composition); (ii) the addition of hydroxyl groups to the 5-, 6- and 7-position of the acridine nucleus diminished the inhibitory potency; and (iii) amsacrine (acridine nucleus with methansulphonanilide side-chain at the 9-position) had no significant inhibitory effect. Similar structural trends were observed for the inhibition of O-de-ethylation of 7-ethoxyresorufin by acridines, supporting the involvement of CYP1A2 in DMXAA 6-methyl hydroxylation. 4. The molecular modelling studies indicated: (i) both DMXAA and N-[2-(dimethylamino)-ethyl]acridine-4-carboxamide (DACA) form two hydrogen bonds plus putative π–π stacking interactions with the CYP1A2-binding domain, typical of CYP1A2 substrates and inhibitors; (ii) the DMXAA 6-methyl group is 4.0 Å from the central iron atom of the heme moiety and ideal for oxidation; (iii) the known oxidation sites for DACA are orientated away from the heme iron, supporting the non-involvement of CYP1A2; and (iv) amsacrine did not fit the putative CYP1A2 site owing to the steric hindrance of the bulky methanesulphonanilide side-chain. 5. These results suggest that docking studies with this homology model may be useful in the design of further acridine anticancer agents, in particular to identify agents that do not interact either as substrates or inhibitors with the CYP1A2-binding domain." @default.
• W1985423401 created "2016-06-24" @default.
• W1985423401 creator A5016932911 @default.
• W1985423401 creator A5033296517 @default.
• W1985423401 creator A5034181458 @default.
• W1985423401 creator A5056011943 @default.
• W1985423401 creator A5089054133 @default.
• W1985423401 date "2005-08-01" @default.
• W1985423401 modified "2023-09-23" @default.
• W1985423401 title "INHIBITION OF HUMAN CYP1A2 OXIDATION OF 5,6-DIMETHYL-XANTHENONE-4-ACETIC ACID BY ACRIDINES: A MOLECULAR MODELLING STUDY" @default.
• W1985423401 cites W1484739867 @default.
• W1985423401 cites W1520201629 @default.
• W1985423401 cites W2027458234 @default.
• W1985423401 cites W2028105139 @default.
• W1985423401 cites W2045941088 @default.
• W1985423401 cites W2047907992 @default.
• W1985423401 cites W2054666489 @default.
• W1985423401 cites W2061163224 @default.
• W1985423401 cites W2071374441 @default.
• W1985423401 cites W2072226612 @default.
• W1985423401 cites W2082630363 @default.
• W1985423401 cites W2087790269 @default.
• W1985423401 cites W2093213782 @default.
• W1985423401 cites W2095635665 @default.
• W1985423401 cites W2120475716 @default.
• W1985423401 cites W2136869792 @default.
• W1985423401 cites W4232534952 @default.
• W1985423401 doi "https://doi.org/10.1111/j.0305-1870.2005.04243.x" @default.
• W1985423401 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16120190" @default.
• W1985423401 hasPublicationYear "2005" @default.
• W1985423401 type Work @default.
• W1985423401 sameAs 1985423401 @default.
• W1985423401 citedByCount "6" @default.
• W1985423401 countsByYear W19854234012013 @default.
• W1985423401 countsByYear W19854234012016 @default.
• W1985423401 crossrefType "journal-article" @default.
• W1985423401 hasAuthorship W1985423401A5016932911 @default.
• W1985423401 hasAuthorship W1985423401A5033296517 @default.
• W1985423401 hasAuthorship W1985423401A5034181458 @default.
• W1985423401 hasAuthorship W1985423401A5056011943 @default.
• W1985423401 hasAuthorship W1985423401A5089054133 @default.
• W1985423401 hasConcept C112887158 @default.
• W1985423401 hasConcept C178790620 @default.
• W1985423401 hasConcept C181199279 @default.
• W1985423401 hasConcept C185592680 @default.
• W1985423401 hasConcept C202751555 @default.
• W1985423401 hasConcept C2776924795 @default.
• W1985423401 hasConcept C2781109383 @default.
• W1985423401 hasConcept C2781338088 @default.
• W1985423401 hasConcept C32909587 @default.
• W1985423401 hasConcept C55493867 @default.
• W1985423401 hasConcept C71240020 @default.
• W1985423401 hasConcept C86745063 @default.
• W1985423401 hasConcept C87644729 @default.
• W1985423401 hasConceptScore W1985423401C112887158 @default.
• W1985423401 hasConceptScore W1985423401C178790620 @default.
• W1985423401 hasConceptScore W1985423401C181199279 @default.
• W1985423401 hasConceptScore W1985423401C185592680 @default.
• W1985423401 hasConceptScore W1985423401C202751555 @default.
• W1985423401 hasConceptScore W1985423401C2776924795 @default.
• W1985423401 hasConceptScore W1985423401C2781109383 @default.
• W1985423401 hasConceptScore W1985423401C2781338088 @default.
• W1985423401 hasConceptScore W1985423401C32909587 @default.
• W1985423401 hasConceptScore W1985423401C55493867 @default.
• W1985423401 hasConceptScore W1985423401C71240020 @default.
• W1985423401 hasConceptScore W1985423401C86745063 @default.
• W1985423401 hasConceptScore W1985423401C87644729 @default.
• W1985423401 hasIssue "8" @default.
• W1985423401 hasLocation W19854234011 @default.
• W1985423401 hasLocation W19854234012 @default.
• W1985423401 hasOpenAccess W1985423401 @default.
• W1985423401 hasPrimaryLocation W19854234011 @default.
• W1985423401 hasRelatedWork W1988026737 @default.
• W1985423401 hasRelatedWork W2022222277 @default.
• W1985423401 hasRelatedWork W2028348957 @default.
• W1985423401 hasRelatedWork W2039980032 @default.
• W1985423401 hasRelatedWork W2055270639 @default.
• W1985423401 hasRelatedWork W2070117143 @default.
• W1985423401 hasRelatedWork W2094542356 @default.
• W1985423401 hasRelatedWork W2145091158 @default.
• W1985423401 hasRelatedWork W2168058034 @default.
• W1985423401 hasRelatedWork W2514368986 @default.
• W1985423401 hasVolume "32" @default.
• W1985423401 isParatext "false" @default.
• W1985423401 isRetracted "false" @default.
• W1985423401 magId "1985423401" @default.
• W1985423401 workType "article" @default.