title: Synthesis, biochemical evaluation and rationalisation of the inhibitory activity of a series of 4-hydroxyphenyl ketones as potential inhibitors of 17beta-hydroxysteroid dehydrogenase type 3 (17beta-HSD3).
abstract: We report the preliminary results of the synthesis and biochemical evaluation of a number of 4-hydroxyphenyl ketones as inhibitors of the isozyme of the enzyme 17beta-hydroxysteroid dehydrogenase (17beta-HSD) responsible for the conversion of androstenedione (AD) to testosterone (T), more specifically type 3 (17beta-HSD3). The results of our study suggest that we have synthesised compounds which are, in general, potent inhibitors of 17beta-HSD3, in particular, we discovered that 1-(4-hydroxy-phenyl)-nonan-1-one (8) was the most potent (IC(50) = 2.86 +/- 0.03 microM). We have therefore provided good lead compounds in the synthesis of novel non-steroidal inhibitors of 17beta-HSD3.
authors.affiliation: Department of Pharmacy, School of Pharmacy and Chemistry, Kingston University, Kingston upon Thames, Surrey, UK.
authors.forename: Rupinder K
authors.initials: RK
authors.lastname: Lota
authors.forename: Sachin
authors.initials: S
authors.lastname: Dhanani
authors.forename: Caroline P
authors.initials: CP
authors.lastname: Owen
authors.forename: Sabbir
authors.initials: S
authors.lastname: Ahmed
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002384:Catalysis; D006859:Hydrogen / Q000737:chemistry*; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure
chemical_list: D007659:Ketones; D006859:Hydrogen; D015067:17-Hydroxysteroid Dehydrogenases; C476565:17beta-hydroxysteroid dehydrogenase type 3