[Asterriquinone derivatives as candidates for new orally available anti-diabetics].
Orally available anti-diabetic candidates, reported by Merck researchers, are reviewed. The lead, asterriquinone B1(1a), was discovered in a fungal extract by screening with the cell line CHO.IR. An analog, 2,5-dihydroxy-3-(1-methylindol-3-yl)-6-phenyl-1,4-benzoquinone(2h), was selected by studying structure-activity relationships with various in vitro and in vivo tests. Analog 2h exhibited selective tyrosin kinase activity to an insulin receptor and a glucose-lowering effect by testing on diabetic rodent models. However, on the basis of the results of in vivo tests on streptozotocin-induced and on normal lean mice, the activity of 2h was attributed to a sensitizing effect on insulin together with an insulin mimetic effect in part. These studies shed light on the search for new anti-diabetic agents by targeting insulin receptors.
Tanaka
J
J
Department of Chemistry, Biology, and Marine Science, University of the Ryukyus.
D000284:Administration, Oral; D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D007004:Hypoglycemic Agents; D045563:Indolequinones; D007211:Indoles / Q000494:pharmacology; D007333:Insulin Resistance; D013329:Structure-Activity Relationship
C444679:2,5-dihydroxy-3-(1-methylindol-3-yl)-6-phenyl-1,4-benzoquinone; D016227:Benzoquinones; D007004:Hypoglycemic Agents; D045563:Indolequinones; D007211:Indoles; C119066:L 783281; C035746:asterriquinone