Creation of readily accessible and orally active analogue of cortistatin A

Naoyuki Kotoku; Yuji Sumii; Takeshi Hayashi; Satoru Tamura; Takashi Kawachi; Sho Shiomura; Masayoshi Arai; Motomasa Kobayashi

doi:10.1021/ml300143d

Creation of readily accessible and orally active analogue of cortistatin A

Naoyuki Kotoku, Yuji Sumii, Takeshi Hayashi, Satoru Tamura, Takashi Kawachi, Sho Shiomura, Masayoshi Arai, Motomasa Kobayashi

SCI - Chemistry

Research output: Contribution to journal › Article › peer-review

11 Citations (Scopus)

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.

Original language	English
Pages (from-to)	673-677
Number of pages	5
Journal	ACS Medicinal Chemistry Letters
Volume	3
Issue number	8
DOIs	https://doi.org/10.1021/ml300143d
Publication status	Published - 2012 Aug 9

Keywords

Cortistatin A
analogue synthesis
antiangiogenesis
marine sponge
structure-activity relationship

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

UN SDGs

This output contributes to the following Sustainable Development Goal(s)

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10.1021/ml300143d

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T1 - Creation of readily accessible and orally active analogue of cortistatin A

AU - Kotoku, Naoyuki

AU - Sumii, Yuji

AU - Hayashi, Takeshi

AU - Tamura, Satoru

AU - Kawachi, Takashi

AU - Shiomura, Sho

AU - Arai, Masayoshi

AU - Kobayashi, Motomasa

PY - 2012/8/9

Y1 - 2012/8/9

N2 - 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.

AB - 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.

KW - Cortistatin A

KW - analogue synthesis

KW - antiangiogenesis

KW - marine sponge

KW - structure-activity relationship

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M3 - Article

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JF - ACS Medicinal Chemistry Letters

SN - 1948-5875

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Creation of readily accessible and orally active analogue of cortistatin A

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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