Daucane phytoestrogens: a structure-activity study.
The estrogenic activity of a series of analogues of the daucane ester ferutinin (1a) modified at the acyl moiety was investigated in a yeast screen containing the human estrogen receptor alpha. Rather strict structure-activity relationships were observed. Thus, while the parent polyol (jaeschkeanadiol, 2a) was inactive, the presence of a p-hydroxybenzoyl moiety was necessary for activity in the yeast screen. Homologation and vinylation were both detrimental for activity, as were methylation of the p-hydroxyl substituent and the introduction of oxygen functions on the adjacent carbons.
Appendino
Giovanni
G
Dipartimento di Scienze Chimiche, Alimentari, Farmaceutiche e Farmacologiche, Università del Piemonte Orientale, Viale Ferrucci 33, 28100 Novara, Italy. appendin@pharm.unito.it
Spagliardi
Paola
P
Cravotto
Giancarlo
G
Pocock
Victoria
V
Milligan
Stuart
S
D001565:Benzoates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001667:Binding, Competitive; D001643:Bridged Bicyclo Compounds; D003508:Cycloheptanes; D004305:Dose-Response Relationship, Drug; D004951:Esterification; D047628:Estrogen Receptor alpha; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D005309:Ferula / Q000737:chemistry*; D006801:Humans; D007529:Isoflavones; D007558:Italy; D048789:Phytoestrogens; D028321:Plant Preparations; D010946:Plants, Medicinal / Q000737:chemistry*; D011960:Receptors, Estrogen / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics; D012717:Sesquiterpenes; D013329:Structure-Activity Relationship
D001565:Benzoates; D001643:Bridged Bicyclo Compounds; D003508:Cycloheptanes; D047628:Estrogen Receptor alpha; D004968:Estrogens, Non-Steroidal; D007529:Isoflavones; D048789:Phytoestrogens; D028321:Plant Preparations; D011960:Receptors, Estrogen; D012717:Sesquiterpenes; C111068:4-oxy-6-(4-oxybezoyloxy)dauc-8,9-en