title: Facile synthesis of chrysin-derivatives with promising activities as aromatase inhibitors.
abstract: Flavones such as chrysin show structural similarities to androgens, the substrates of human aromatase, which converts androgens to estrogens. Aromatase is a key target in the treatment of hormone-dependent tumors, including breast cancer. Flavone-based aromatase inhibitors are of growing interest, and chrysin in particular provides a (natural) lead structure. This paper reports multicomponent synthesis as a means for facile modification of the chrysin core structure in order to add functional elements. A Mannich-type reaction was used to synthesize a range of mono- and disubstituted chrysin derivatives, some of which are more effective aromatase inhibitors than the benchmark compound, aminoglutethimide. Similarly, the reaction of chrysin with various isonitriles and acetylene dicarboxylates results in a new class of flavone derivatives, tricyclic pyrano-flavones which also inhibit human aromatase. Multicomponent reactions involving flavones therefore enable the synthesis of a variety of derivatives, some of which may be useful as anticancer agents.
authors.affiliation: Division of Bioorganic Chemistry, School ofPharmacy, Saarland University, P.O. Box 151150, D-66123 Saarbruecken, Germany.
authors.forename: Hamdoon A
authors.initials: HA
authors.lastname: Mohammed
authors.forename: Lalla A
authors.initials: LA
authors.lastname: Ba
authors.forename: Torsten
authors.initials: T
authors.lastname: Burkholz
authors.forename: Elena
authors.initials: E
authors.lastname: Schumann
authors.forename: Britta
authors.initials: B
authors.lastname: Diesel
authors.forename: Josef
authors.initials: J
authors.lastname: Zapp
authors.forename: Alexandra K
authors.initials: AK
authors.lastname: Kiemer
authors.forename: Christina
authors.initials: C
authors.lastname: Ries
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Hartmann
authors.forename: Mohammed
authors.initials: M
authors.lastname: Hosny
authors.forename: Claus
authors.initials: C
authors.lastname: Jacob
mesh_terms: D047072:Aromatase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005419:Flavonoids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D012995:Solubility
chemical_list: D047072:Aromatase Inhibitors; D005419:Flavonoids; C043561:chrysin