title: Creation of readily accessible and orally active analogue of cortistatin a.
abstract: Syntheses of structurally simplified analogues of cortistatin A (1), a novel antiangiogenic steroidal alkaloid from Indonesian marine sponge, and their biological activities were investigated. The analogues were designed by considering the 3-D structure of 1. Compound 30, in which the isoquinoline moiety was appended to the planar tetracyclic core structure, showed potent antiproliferative activity against human umbilical vein endothelial cells (HUVECs) together with high selectivity and also showed in vivo antiangiogenic activity and significant antitumor effect by oral administration.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University , 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kotoku
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University , 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sumii
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University , 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University , 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Tamura
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University , 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kawachi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University , 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Shiomura
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University , 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Arai
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University , 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Motomasa
authors.initials: M
authors.lastname: Kobayashi
keywords: Cortistatin A; analogue synthesis; antiangiogenesis; marine sponge; structure−activity relationship