2. Academic Validation
  3. Synthesis and pharmacological evaluation of novel non-lactone analogues of camptothecin

Synthesis and pharmacological evaluation of novel non-lactone analogues of camptothecin

  • Bioorg Med Chem Lett. 2003 Aug 18;13(16):2731-5. doi: 10.1016/s0960-894x(03)00534-1.
Patrick Hautefaye 1,  Bernard Cimetière,  Alain Pierré,  Stéphane Léonce,  John Hickman,  William Laine,  Christian Bailly,  Gilbert Lavielle
Affiliations

Affiliation

  • 1 Institut de Recherches Servier, 125 Chemin de Ronde, 78290, Croissy sur Seine, France.
PMID: 12873503 DOI: 10.1016/s0960-894x(03)00534-1
Abstract

Ten novel camptothecin (CPT) derivatives devoid of the lactone function in the E-ring were synthesized and evaluated as Anticancer agents. Several of these CPT analogues bearing a five-membered E-ring are potent inhibitors of the DNA relaxation and cleavage reactions catalyzed by Topoisomerase I and exhibit promising cytotoxic activities with IC(50) values in the nM range. This is the first successful design of lactone-free CPT, providing thus a new avenue to the development of Topoisomerase I targeted antitumor agents.

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