Authors: Galmarini, C. M.; Popowycz, F.; Joseph, B.

Source: Current Medicinal Chemistry, Volume 15, Number 11, May 2008 , pp. 1072-1082(11)

Publisher: Bentham Science Publishers

Abstract:

Cytotoxic nucleoside analogues are clinically important anticancer drugs. These agents behave as antimetabolites, compete with physiologic nucleosides, and, consequently, interact with a large number of intracellular targets to induce cytotoxicity. Nucleoside analogues share some general common characteristics, namely in terms of requiring transport by specific membrane transporters and intracellular metabolism. However these compounds differ in regard to the preferential interaction with certain targets which may explain why some compounds are more effective against rapidly proliferating tumours and others on neoplasia with a more protracted evolution. Purine and pyrimidine analogues are widely used not only as antileukaemic agents, but also as cytotoxic agents to treat solid tumours. However, the clinical use of these compounds is limited by important side-effects and primary or acquired drug resistance. Thus, there is an unmet medical need for the development of new antimetabolites and for technologies allowing a more suitable and effective administration of nucleoside analogues for the treatment of cancer patients. Here, we will review literature data concerning the recent development of novel purine nucleoside analogues (clofarabine, nelarabine and forodesine) and pyrimidine nucleoside analogues (troxacitabine, sapacitabine, CP-4055, 3'-C-ethynylcytidine and 5-azapyrimidines) that are in evaluation at the clinical level.

Keywords: Antimetabolites; purine nucleosides; pyrimidine nucleosides; clofarabine; nelarabine; forodesine; troxacitabine; sapacitabine; 3'-C-ethynylcytidine; 5-azacytidine

Document Type: Research article

Affiliations: 1: ENS-CNRS UMR 5239 - U.F.R. de Medecine Lyon-Sud, 165 chemin du Grand Revoyet BP12 - 69921 - Oullins Cedex,France.

Publication date: 2008-05-01

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• Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

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