Macrocyclic hexaoxazoles: Influence of aminoalkyl substituents on RNA and DNA G-quadruplex stabilization and cytotoxicity

Mavurapu Satyanarayana; Young Ah Kim; Suzanne G. Rzuczek; Daniel S. Pilch; Angela A. Liu; Leroy F. Liu; Joseph E. Rice; Edmond J. LaVoie

doi:10.1016/j.bmcl.2010.03.086

Macrocyclic hexaoxazoles: Influence of aminoalkyl substituents on RNA and DNA G-quadruplex stabilization and cytotoxicity

Mavurapu Satyanarayana, Young Ah Kim, Suzanne G. Rzuczek, Daniel S. Pilch, Angela A. Liu, Leroy F. Liu, Joseph E. Rice, Edmond J. LaVoie

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

28 Citations (Scopus)

Abstract

A series of 24-membered macrocyclic hexaoxazoles containing one or two aminoalkyl substituents was synthesized and evaluated for cytotoxicity and for their ability to selectively stabilize G-quadruplex DNA and RNA. The most cytotoxic analog 4a, with IC₅₀ values of 25 and 130 nM using KB3-1 and RPMI 8402 cells, is efficacious in vivo in athymic nude mice with a human tumor xenograft from the breast cancer cell line MDA-MB-435.

Original language	English
Pages (from-to)	3150-3154
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	20
Issue number	10
DOIs	https://doi.org/10.1016/j.bmcl.2010.03.086
Publication status	Published - May 15 2010
Externally published	Yes

Keywords

Antitumor
Athymic nude mice
Cytotoxicity
G-quadruplex DNA
G-quadruplex RNA
G-quadruplex ligands
Hexaoxazoles
MDA-MB-435 xenograft
Macrocycles

ASJC Scopus subject areas

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmcl.2010.03.086

Cite this

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title = "Macrocyclic hexaoxazoles: Influence of aminoalkyl substituents on RNA and DNA G-quadruplex stabilization and cytotoxicity",

abstract = "A series of 24-membered macrocyclic hexaoxazoles containing one or two aminoalkyl substituents was synthesized and evaluated for cytotoxicity and for their ability to selectively stabilize G-quadruplex DNA and RNA. The most cytotoxic analog 4a, with IC50 values of 25 and 130 nM using KB3-1 and RPMI 8402 cells, is efficacious in vivo in athymic nude mice with a human tumor xenograft from the breast cancer cell line MDA-MB-435.",

keywords = "Antitumor, Athymic nude mice, Cytotoxicity, G-quadruplex DNA, G-quadruplex RNA, G-quadruplex ligands, Hexaoxazoles, MDA-MB-435 xenograft, Macrocycles",

author = "Mavurapu Satyanarayana and Kim, {Young Ah} and Rzuczek, {Suzanne G.} and Pilch, {Daniel S.} and Liu, {Angela A.} and Liu, {Leroy F.} and Rice, {Joseph E.} and LaVoie, {Edmond J.}",

year = "2010",

month = may,

day = "15",

doi = "10.1016/j.bmcl.2010.03.086",

language = "English",

volume = "20",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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T1 - Macrocyclic hexaoxazoles

T2 - Influence of aminoalkyl substituents on RNA and DNA G-quadruplex stabilization and cytotoxicity

AU - Satyanarayana, Mavurapu

AU - Kim, Young Ah

AU - Rzuczek, Suzanne G.

AU - Pilch, Daniel S.

AU - Liu, Angela A.

AU - Liu, Leroy F.

AU - Rice, Joseph E.

AU - LaVoie, Edmond J.

PY - 2010/5/15

Y1 - 2010/5/15

N2 - A series of 24-membered macrocyclic hexaoxazoles containing one or two aminoalkyl substituents was synthesized and evaluated for cytotoxicity and for their ability to selectively stabilize G-quadruplex DNA and RNA. The most cytotoxic analog 4a, with IC50 values of 25 and 130 nM using KB3-1 and RPMI 8402 cells, is efficacious in vivo in athymic nude mice with a human tumor xenograft from the breast cancer cell line MDA-MB-435.

AB - A series of 24-membered macrocyclic hexaoxazoles containing one or two aminoalkyl substituents was synthesized and evaluated for cytotoxicity and for their ability to selectively stabilize G-quadruplex DNA and RNA. The most cytotoxic analog 4a, with IC50 values of 25 and 130 nM using KB3-1 and RPMI 8402 cells, is efficacious in vivo in athymic nude mice with a human tumor xenograft from the breast cancer cell line MDA-MB-435.

KW - Antitumor

KW - Athymic nude mice

KW - Cytotoxicity

KW - G-quadruplex DNA

KW - G-quadruplex RNA

KW - G-quadruplex ligands

KW - Hexaoxazoles

KW - MDA-MB-435 xenograft

KW - Macrocycles

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M3 - Article

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SN - 0960-894X

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JO - Bioorganic and Medicinal Chemistry Letters

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Macrocyclic hexaoxazoles: Influence of aminoalkyl substituents on RNA and DNA G-quadruplex stabilization and cytotoxicity

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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