Author/Editor		Sova, Matej; Perdih, Andrej; Kotnik, Miha; Kristan, Katja; Lanišnik-Rižner, Tea; Šolmajer, Tom; Gobec, Stanislav
Title		Flavonoids and cinnamic acid esters as inhibitors of fungal 17beta-hydroxysteroid dehydrogenase: a synthesis, QSAR and modelling study
Type		članek
Source		Bioorg Med Chem
Vol. and No.		Letnik 14, št. 22
Publication year		2006
Volume		str. 7404-18
Language		eng
Abstract		The 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) modulate the biological potency of estrogens and androgens by interconversion of inactive 17-keto-steroids and their active 17beta-hydroxy- counterparts. We have shown previously that flavonoids are potentially useful lead compounds for developing inhibitors of 17beta-HSDs. In this paper, we describe the synthesis and biochemical evaluation of structurally analogous inhibitors, the traps-cinnamic acid esters and related compounds. Additionally, quantitative structure-activity relationship (QSAR) and modelling studies were performed to rationalize the results and to suggest further optimization. The results stress the importance of a hydrogen bond with Asn154 and hydrophobic interactions with the aromatic side chain of Tyr212 for optimal molecular recognition.
Descriptors		ASCOMYCETES FLAVONES CINNAMATES 17-HYDROXYSTEROID DEHYDROGENASES ENZYME INHIBITORS RECOMBINANT PROTEINS