Ring-closing metathesis for the synthesis of a highly G-quadruplex selective macrocyclic hexaoxazole having enhanced cytotoxic potency

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

doi:10.1016/j.bmcl.2008.05.032

Ring-closing metathesis for the synthesis of a highly G-quadruplex selective macrocyclic hexaoxazole having enhanced cytotoxic potency

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

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

30 Citations (Scopus)

Abstract

The synthesis of a 24-membered macrocyclic hexaoxazole via ring-closing metathesis is described. The target compound selectively stabilizes G-quadruplex DNA with no detectable stabilization of duplex DNA. An MTT cytotoxicity assay indicated that this unsaturated macrocyclic hexaoxazole exhibits significant cytotoxicity toward P388, RPMI 8402, and KB3-1 cell lines with IC₅₀ values of 45, 25, and 38 nM, respectively.

Original language	English
Pages (from-to)	3802-3804
Number of pages	3
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	18
Issue number	13
DOIs	https://doi.org/10.1016/j.bmcl.2008.05.032
Publication status	Published - Jul 1 2008
Externally published	Yes

Keywords

Cytotoxic
G-quadruplex stabilizer
Hexaoxazole
Macrocycle
Ring-closing metathesis
Selective
Synthesis

ASJC Scopus subject areas

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

Access to Document

10.1016/j.bmcl.2008.05.032

Cite this

@article{e623005e06874987bf72377220fcb952,

title = "Ring-closing metathesis for the synthesis of a highly G-quadruplex selective macrocyclic hexaoxazole having enhanced cytotoxic potency",

abstract = "The synthesis of a 24-membered macrocyclic hexaoxazole via ring-closing metathesis is described. The target compound selectively stabilizes G-quadruplex DNA with no detectable stabilization of duplex DNA. An MTT cytotoxicity assay indicated that this unsaturated macrocyclic hexaoxazole exhibits significant cytotoxicity toward P388, RPMI 8402, and KB3-1 cell lines with IC50 values of 45, 25, and 38 nM, respectively.",

keywords = "Cytotoxic, G-quadruplex stabilizer, Hexaoxazole, Macrocycle, Ring-closing metathesis, Selective, Synthesis",

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

note = "Funding Information: This study was supported by generous funding from Celgene Corp. and NIH Grants CA098127 (E.J.L.) and CA097123 (D.S.P.). Mass spectrometry was provided by the Washington University Mass Spectrometry Resource with support from the NIH National Center for Research Resources Grant P41RR0954.",

year = "2008",

month = jul,

day = "1",

doi = "10.1016/j.bmcl.2008.05.032",

language = "English",

volume = "18",

pages = "3802--3804",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd",

number = "13",

}

TY - JOUR

T1 - Ring-closing metathesis for the synthesis of a highly G-quadruplex selective macrocyclic hexaoxazole having enhanced cytotoxic potency

AU - Satyanarayana, Mavurapu

AU - Rzuczek, Suzanne G.

AU - LaVoie, Edmond J.

AU - Pilch, Daniel S.

AU - Liu, Angela

AU - Liu, Leroy F.

AU - Rice, Joseph E.

N1 - Funding Information: This study was supported by generous funding from Celgene Corp. and NIH Grants CA098127 (E.J.L.) and CA097123 (D.S.P.). Mass spectrometry was provided by the Washington University Mass Spectrometry Resource with support from the NIH National Center for Research Resources Grant P41RR0954.

PY - 2008/7/1

Y1 - 2008/7/1

N2 - The synthesis of a 24-membered macrocyclic hexaoxazole via ring-closing metathesis is described. The target compound selectively stabilizes G-quadruplex DNA with no detectable stabilization of duplex DNA. An MTT cytotoxicity assay indicated that this unsaturated macrocyclic hexaoxazole exhibits significant cytotoxicity toward P388, RPMI 8402, and KB3-1 cell lines with IC50 values of 45, 25, and 38 nM, respectively.

AB - The synthesis of a 24-membered macrocyclic hexaoxazole via ring-closing metathesis is described. The target compound selectively stabilizes G-quadruplex DNA with no detectable stabilization of duplex DNA. An MTT cytotoxicity assay indicated that this unsaturated macrocyclic hexaoxazole exhibits significant cytotoxicity toward P388, RPMI 8402, and KB3-1 cell lines with IC50 values of 45, 25, and 38 nM, respectively.

KW - Cytotoxic

KW - G-quadruplex stabilizer

KW - Hexaoxazole

KW - Macrocycle

KW - Ring-closing metathesis

KW - Selective

KW - Synthesis

UR - https://www.scopus.com/pages/publications/44849098127

UR - https://www.scopus.com/pages/publications/44849098127#tab=citedBy

U2 - 10.1016/j.bmcl.2008.05.032

DO - 10.1016/j.bmcl.2008.05.032

M3 - Article

C2 - 18515097

AN - SCOPUS:44849098127

SN - 0960-894X

VL - 18

SP - 3802

EP - 3804

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 13

ER -

Ring-closing metathesis for the synthesis of a highly G-quadruplex selective macrocyclic hexaoxazole having enhanced cytotoxic potency

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this