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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:18

Article

Satyanarayana, Mavurapu¹  Rzuczek, Suzanne G.¹  LaVoie, Edmond J.^1,3  Pilch, Daniel S.^2,3  Liu, Angela^2,3  Liu, Leroy F.^2,3  Rice, Joseph E.¹ 

[1] Rutgers State Univ, Ernest Mario Sch Pharm, Dept Pharmaceut Chem, Piscataway, NJ 08854 USA

[2] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pharmacol, Piscataway, NJ 08901 USA

[3] Inst Canc Res, New Brunswick, NJ 08901 USA

关键词: synthesis;    macrocycle;    hexaoxazole;    cytotoxic;    G-quadruplex stabilizer;    ring-closing metathesis;    selective;   

DOI  :  10.1016/j.bmcl.2008.05.032

来源: Elsevier

【 摘 要 】

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 IC(50) values of 45, 25, and 38 nM, respectively. (c) 2008 Elsevier Ltd. All rights reserved.

【 授权许可】

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