Macrocyclic biphenyl tetraoxazoles: Synthesis, evaluation as G-quadruplex stabilizers and cytotoxic activity

Gifty A. Blankson, Daniel S. Pilch, Angela A. Liu, Leroy-Fong Liu, Joseph E. Rice, Edmond J. Lavoie

研究成果: 雜誌貢獻文章

10 引文 (Scopus)

摘要

A series of macrocyclic biphenyl tetraoxazoles was synthesized. The latter stages of the synthetic approach allowed for the addition of varied N-protected α-amino acids, which were subsequently deprotected and condensed to provide the desired macrocycles. Improved yields could be realized in the macrocyclization step of their synthesis relative to other macrocyclic G-quadruplex stabilizers. These 24-membered macrocycles were evaluated for their ability to stabilize G-quadruplex DNA and for their relative cytotoxicity against human tumor cells. These biphenyl tetraoxazoles were not strong ligands for G-quadruplex DNA relative to other macrocyclic polyoxazoles. This reduced stabilizing potential did correlate with their comparatively lower cytotoxic activity as observed in the human tumor cell lines, RPMI 8402 and KB3-1. These studies provide useful insights into the conformational requirements for the development of selective and more potent G-quadruplex ligands.

原文英語
頁(從 - 到)4511-4520
頁數10
期刊Bioorganic and Medicinal Chemistry
21
發行號15
DOIs
出版狀態已發佈 - 八月 1 2013
對外發佈Yes

指紋

G-Quadruplexes
Tumors
Cells
Ligands
DNA
Cytotoxicity
Amino Acids
Tumor Cell Line
diphenyl
Neoplasms

ASJC Scopus subject areas

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

引用此文

Macrocyclic biphenyl tetraoxazoles : Synthesis, evaluation as G-quadruplex stabilizers and cytotoxic activity. / Blankson, Gifty A.; Pilch, Daniel S.; Liu, Angela A.; Liu, Leroy-Fong; Rice, Joseph E.; Lavoie, Edmond J.

於: Bioorganic and Medicinal Chemistry, 卷 21, 編號 15, 01.08.2013, p. 4511-4520.

研究成果: 雜誌貢獻文章

Blankson, Gifty A. ; Pilch, Daniel S. ; Liu, Angela A. ; Liu, Leroy-Fong ; Rice, Joseph E. ; Lavoie, Edmond J. / Macrocyclic biphenyl tetraoxazoles : Synthesis, evaluation as G-quadruplex stabilizers and cytotoxic activity. 於: Bioorganic and Medicinal Chemistry. 2013 ; 卷 21, 編號 15. 頁 4511-4520.
@article{747f3936df264b898af19e790a15027f,
title = "Macrocyclic biphenyl tetraoxazoles: Synthesis, evaluation as G-quadruplex stabilizers and cytotoxic activity",
abstract = "A series of macrocyclic biphenyl tetraoxazoles was synthesized. The latter stages of the synthetic approach allowed for the addition of varied N-protected α-amino acids, which were subsequently deprotected and condensed to provide the desired macrocycles. Improved yields could be realized in the macrocyclization step of their synthesis relative to other macrocyclic G-quadruplex stabilizers. These 24-membered macrocycles were evaluated for their ability to stabilize G-quadruplex DNA and for their relative cytotoxicity against human tumor cells. These biphenyl tetraoxazoles were not strong ligands for G-quadruplex DNA relative to other macrocyclic polyoxazoles. This reduced stabilizing potential did correlate with their comparatively lower cytotoxic activity as observed in the human tumor cell lines, RPMI 8402 and KB3-1. These studies provide useful insights into the conformational requirements for the development of selective and more potent G-quadruplex ligands.",
keywords = "Biphenyl, Cytotoxicity, G-quadruplex, G-quadruplex ligand, Macrocycle, Oxazoles",
author = "Blankson, {Gifty A.} and Pilch, {Daniel S.} and Liu, {Angela A.} and Leroy-Fong Liu and Rice, {Joseph E.} and Lavoie, {Edmond J.}",
year = "2013",
month = "8",
day = "1",
doi = "10.1016/j.bmc.2013.05.033",
language = "English",
volume = "21",
pages = "4511--4520",
journal = "Bioorganic and Medicinal Chemistry",
issn = "0968-0896",
publisher = "Elsevier Limited",
number = "15",

}

TY - JOUR

T1 - Macrocyclic biphenyl tetraoxazoles

T2 - Synthesis, evaluation as G-quadruplex stabilizers and cytotoxic activity

AU - Blankson, Gifty A.

AU - Pilch, Daniel S.

AU - Liu, Angela A.

AU - Liu, Leroy-Fong

AU - Rice, Joseph E.

AU - Lavoie, Edmond J.

PY - 2013/8/1

Y1 - 2013/8/1

N2 - A series of macrocyclic biphenyl tetraoxazoles was synthesized. The latter stages of the synthetic approach allowed for the addition of varied N-protected α-amino acids, which were subsequently deprotected and condensed to provide the desired macrocycles. Improved yields could be realized in the macrocyclization step of their synthesis relative to other macrocyclic G-quadruplex stabilizers. These 24-membered macrocycles were evaluated for their ability to stabilize G-quadruplex DNA and for their relative cytotoxicity against human tumor cells. These biphenyl tetraoxazoles were not strong ligands for G-quadruplex DNA relative to other macrocyclic polyoxazoles. This reduced stabilizing potential did correlate with their comparatively lower cytotoxic activity as observed in the human tumor cell lines, RPMI 8402 and KB3-1. These studies provide useful insights into the conformational requirements for the development of selective and more potent G-quadruplex ligands.

AB - A series of macrocyclic biphenyl tetraoxazoles was synthesized. The latter stages of the synthetic approach allowed for the addition of varied N-protected α-amino acids, which were subsequently deprotected and condensed to provide the desired macrocycles. Improved yields could be realized in the macrocyclization step of their synthesis relative to other macrocyclic G-quadruplex stabilizers. These 24-membered macrocycles were evaluated for their ability to stabilize G-quadruplex DNA and for their relative cytotoxicity against human tumor cells. These biphenyl tetraoxazoles were not strong ligands for G-quadruplex DNA relative to other macrocyclic polyoxazoles. This reduced stabilizing potential did correlate with their comparatively lower cytotoxic activity as observed in the human tumor cell lines, RPMI 8402 and KB3-1. These studies provide useful insights into the conformational requirements for the development of selective and more potent G-quadruplex ligands.

KW - Biphenyl

KW - Cytotoxicity

KW - G-quadruplex

KW - G-quadruplex ligand

KW - Macrocycle

KW - Oxazoles

UR - http://www.scopus.com/inward/record.url?scp=84879693733&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84879693733&partnerID=8YFLogxK

U2 - 10.1016/j.bmc.2013.05.033

DO - 10.1016/j.bmc.2013.05.033

M3 - Article

C2 - 23787291

AN - SCOPUS:84879693733

VL - 21

SP - 4511

EP - 4520

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

SN - 0968-0896

IS - 15

ER -