Design, synthesis and biological evaluation of photoaffinity probes of antiangiogenic homoisoflavonoids

Bit Lee, Wei Sun, Hyungjun Lee, Halesha Basavarajappa, Rania S. Sulaiman, Kamakshi Sishtla, Xiang Fei, Timothy Corson, Seung Yong Seo

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

A naturally occurring homoisoflavonoid, cremastranone (1) inhibited angiogenesis in vitro and in vivo. We developed an analogue SH-11037 (2) which is more potent than cremastranone in human retinal microvascular endothelial cells (HRECs) and blocks neovascularization in animal models. Despite their efficacy, the mechanism of these compounds is not yet fully known. In the course of building on a strong foundation of SAR and creating a novel chemical tool for target identification of homoisoflavonoid-binding proteins, various types of photoaffinity probes were designed and synthesized in which benzophenone and biotin were attached to homoisoflavanonoids using PEG linkers on either the C-3′ or C-7 position. Notably, the photoaffinity probes linking on the phenol group of the C-3′ position retain excellent activity of inhibiting retinal endothelial cell proliferation with up to 72 nM of GI50.

Original languageEnglish (US)
Pages (from-to)4277-4281
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume26
Issue number17
DOIs
StatePublished - Sep 1 2016

Fingerprint

Endothelial cells
Endothelial Cells
Cell proliferation
Biotin
Phenol
Polyethylene glycols
Carrier Proteins
Animals
Animal Models
Cell Proliferation
5,7-dihydroxy-3-(3-hydroxy-4-methoxybenzyl)-6-methoxychroman-4-one
benzophenone
In Vitro Techniques

Keywords

  • Antiangiogenic agents
  • Homoisoflavonoids
  • Human retinal microvascular endothelial cells
  • Photoaffinity probes
  • Wet age-related macular degeneration

ASJC Scopus subject areas

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

Cite this

Design, synthesis and biological evaluation of photoaffinity probes of antiangiogenic homoisoflavonoids. / Lee, Bit; Sun, Wei; Lee, Hyungjun; Basavarajappa, Halesha; Sulaiman, Rania S.; Sishtla, Kamakshi; Fei, Xiang; Corson, Timothy; Seo, Seung Yong.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 26, No. 17, 01.09.2016, p. 4277-4281.

Research output: Contribution to journalArticle

Lee, Bit ; Sun, Wei ; Lee, Hyungjun ; Basavarajappa, Halesha ; Sulaiman, Rania S. ; Sishtla, Kamakshi ; Fei, Xiang ; Corson, Timothy ; Seo, Seung Yong. / Design, synthesis and biological evaluation of photoaffinity probes of antiangiogenic homoisoflavonoids. In: Bioorganic and Medicinal Chemistry Letters. 2016 ; Vol. 26, No. 17. pp. 4277-4281.
@article{d68c9e6c3a054702b621dc828bfe32db,
title = "Design, synthesis and biological evaluation of photoaffinity probes of antiangiogenic homoisoflavonoids",
abstract = "A naturally occurring homoisoflavonoid, cremastranone (1) inhibited angiogenesis in vitro and in vivo. We developed an analogue SH-11037 (2) which is more potent than cremastranone in human retinal microvascular endothelial cells (HRECs) and blocks neovascularization in animal models. Despite their efficacy, the mechanism of these compounds is not yet fully known. In the course of building on a strong foundation of SAR and creating a novel chemical tool for target identification of homoisoflavonoid-binding proteins, various types of photoaffinity probes were designed and synthesized in which benzophenone and biotin were attached to homoisoflavanonoids using PEG linkers on either the C-3′ or C-7 position. Notably, the photoaffinity probes linking on the phenol group of the C-3′ position retain excellent activity of inhibiting retinal endothelial cell proliferation with up to 72 nM of GI50.",
keywords = "Antiangiogenic agents, Homoisoflavonoids, Human retinal microvascular endothelial cells, Photoaffinity probes, Wet age-related macular degeneration",
author = "Bit Lee and Wei Sun and Hyungjun Lee and Halesha Basavarajappa and Sulaiman, {Rania S.} and Kamakshi Sishtla and Xiang Fei and Timothy Corson and Seo, {Seung Yong}",
year = "2016",
month = "9",
day = "1",
doi = "10.1016/j.bmcl.2016.07.043",
language = "English (US)",
volume = "26",
pages = "4277--4281",
journal = "Bioorganic and Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Elsevier Limited",
number = "17",

}

TY - JOUR

T1 - Design, synthesis and biological evaluation of photoaffinity probes of antiangiogenic homoisoflavonoids

AU - Lee, Bit

AU - Sun, Wei

AU - Lee, Hyungjun

AU - Basavarajappa, Halesha

AU - Sulaiman, Rania S.

AU - Sishtla, Kamakshi

AU - Fei, Xiang

AU - Corson, Timothy

AU - Seo, Seung Yong

PY - 2016/9/1

Y1 - 2016/9/1

N2 - A naturally occurring homoisoflavonoid, cremastranone (1) inhibited angiogenesis in vitro and in vivo. We developed an analogue SH-11037 (2) which is more potent than cremastranone in human retinal microvascular endothelial cells (HRECs) and blocks neovascularization in animal models. Despite their efficacy, the mechanism of these compounds is not yet fully known. In the course of building on a strong foundation of SAR and creating a novel chemical tool for target identification of homoisoflavonoid-binding proteins, various types of photoaffinity probes were designed and synthesized in which benzophenone and biotin were attached to homoisoflavanonoids using PEG linkers on either the C-3′ or C-7 position. Notably, the photoaffinity probes linking on the phenol group of the C-3′ position retain excellent activity of inhibiting retinal endothelial cell proliferation with up to 72 nM of GI50.

AB - A naturally occurring homoisoflavonoid, cremastranone (1) inhibited angiogenesis in vitro and in vivo. We developed an analogue SH-11037 (2) which is more potent than cremastranone in human retinal microvascular endothelial cells (HRECs) and blocks neovascularization in animal models. Despite their efficacy, the mechanism of these compounds is not yet fully known. In the course of building on a strong foundation of SAR and creating a novel chemical tool for target identification of homoisoflavonoid-binding proteins, various types of photoaffinity probes were designed and synthesized in which benzophenone and biotin were attached to homoisoflavanonoids using PEG linkers on either the C-3′ or C-7 position. Notably, the photoaffinity probes linking on the phenol group of the C-3′ position retain excellent activity of inhibiting retinal endothelial cell proliferation with up to 72 nM of GI50.

KW - Antiangiogenic agents

KW - Homoisoflavonoids

KW - Human retinal microvascular endothelial cells

KW - Photoaffinity probes

KW - Wet age-related macular degeneration

UR - http://www.scopus.com/inward/record.url?scp=84981347705&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84981347705&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2016.07.043

DO - 10.1016/j.bmcl.2016.07.043

M3 - Article

C2 - 27481561

AN - SCOPUS:84981347705

VL - 26

SP - 4277

EP - 4281

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 17

ER -