Anti-invasive and anti-angiogenic activities of naturally occurring dibenzodiazepine BU-4664L and its derivatives

Satoshi Miyanaga; Hiroaki Sakurai; Ikuo Saiki; Hiroyasu Onaka; Yasuhiro Igarashi

doi:10.1016/j.bmcl.2009.12.055

Anti-invasive and anti-angiogenic activities of naturally occurring dibenzodiazepine BU-4664L and its derivatives

Satoshi Miyanaga, Hiroaki Sakurai, Ikuo Saiki, Hiroyasu Onaka, Yasuhiro Igarashi^*

^*Corresponding author for this work

Cancer Cell Biology

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

25 Scopus citations

Abstract

In the screening for antitumor leads from microbial secondary metabolites, BU-4664L (1), a naturally occurring dibenzodiazepine, was found to inhibit tumor invasion and angiogenesis in vitro. Compound 1 inhibited the gelatinase activities of MMP-2 and MMP-9 and the cellular motility. Four derivatives (2-5) were synthesized from 1 and their antitumor activities were evaluated. Compounds 3 and 4 exhibited potent anti-angiogenic effects on HUVEC, together with remarkable inhibition of cell migration at nanomolar concentrations, and showed much lower cytotoxicity.

Original language	English
Pages (from-to)	963-965
Number of pages	3
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	20
Issue number	3
DOIs	https://doi.org/10.1016/j.bmcl.2009.12.055
State	Published - 2010/02/01

Keywords

Angiogenesis
BU-4664L
Dibenzodiazepine
Invasion

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2009.12.055

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title = "Anti-invasive and anti-angiogenic activities of naturally occurring dibenzodiazepine BU-4664L and its derivatives",

abstract = "In the screening for antitumor leads from microbial secondary metabolites, BU-4664L (1), a naturally occurring dibenzodiazepine, was found to inhibit tumor invasion and angiogenesis in vitro. Compound 1 inhibited the gelatinase activities of MMP-2 and MMP-9 and the cellular motility. Four derivatives (2-5) were synthesized from 1 and their antitumor activities were evaluated. Compounds 3 and 4 exhibited potent anti-angiogenic effects on HUVEC, together with remarkable inhibition of cell migration at nanomolar concentrations, and showed much lower cytotoxicity.",

keywords = "Angiogenesis, BU-4664L, Dibenzodiazepine, Invasion",

author = "Satoshi Miyanaga and Hiroaki Sakurai and Ikuo Saiki and Hiroyasu Onaka and Yasuhiro Igarashi",

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T1 - Anti-invasive and anti-angiogenic activities of naturally occurring dibenzodiazepine BU-4664L and its derivatives

AU - Miyanaga, Satoshi

AU - Sakurai, Hiroaki

AU - Saiki, Ikuo

AU - Onaka, Hiroyasu

AU - Igarashi, Yasuhiro

PY - 2010/2/1

Y1 - 2010/2/1

N2 - In the screening for antitumor leads from microbial secondary metabolites, BU-4664L (1), a naturally occurring dibenzodiazepine, was found to inhibit tumor invasion and angiogenesis in vitro. Compound 1 inhibited the gelatinase activities of MMP-2 and MMP-9 and the cellular motility. Four derivatives (2-5) were synthesized from 1 and their antitumor activities were evaluated. Compounds 3 and 4 exhibited potent anti-angiogenic effects on HUVEC, together with remarkable inhibition of cell migration at nanomolar concentrations, and showed much lower cytotoxicity.

AB - In the screening for antitumor leads from microbial secondary metabolites, BU-4664L (1), a naturally occurring dibenzodiazepine, was found to inhibit tumor invasion and angiogenesis in vitro. Compound 1 inhibited the gelatinase activities of MMP-2 and MMP-9 and the cellular motility. Four derivatives (2-5) were synthesized from 1 and their antitumor activities were evaluated. Compounds 3 and 4 exhibited potent anti-angiogenic effects on HUVEC, together with remarkable inhibition of cell migration at nanomolar concentrations, and showed much lower cytotoxicity.

KW - Angiogenesis

KW - BU-4664L

KW - Dibenzodiazepine

KW - Invasion

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DO - 10.1016/j.bmcl.2009.12.055

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SN - 0960-894X

VL - 20

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JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 3

ER -

Anti-invasive and anti-angiogenic activities of naturally occurring dibenzodiazepine BU-4664L and its derivatives

Abstract

Keywords

ASJC Scopus subject areas

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