title: Invention of anti-Leishmania drugs on the basis of the nucleoside structures.
abstract: 3'-Deoxy-3'-fluoroinosine is a potent inhibitor for the growth of the promastigote form of Leishmania tropica and Leishmania donovani. In culture, the EC50 values of 3'-deoxy-3'-fluoroinosine are 2.3 x 10(-7) and 1.0 x 10(-6) M for the promastigotes of L. tropica and L. donovani, respectively. It is less toxic towards mouse mammary tumor FM3A cells: the EC50 value is 2.0 x 10(-4) M. 3'-Deoxy-3'-fluoroinosine is metabolized by Leishmania promastigotes to give 3'-deoxy-3'-fluoroadenosine-5'-triphosphate. This metabolic conversion provides a mechanism for the parasite-selective toxicity of 3'-deoxy-3'-fluoroinosine.
authors.affiliation: Faculty of Pharmaceutical Sciences, Okayama University, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Wataya
authors.forename: H
authors.initials: H
authors.lastname: Tanifuji
authors.forename: F
authors.initials: F
authors.lastname: Kubochi
authors.forename: A
authors.initials: A
authors.lastname: Yoshioka-Hiramoto
authors.forename: K
authors.initials: K
authors.lastname: Morishige
authors.forename: A
authors.initials: A
authors.lastname: Ishii
authors.forename: Y
authors.initials: Y
authors.lastname: Morizawa
authors.forename: T
authors.initials: T
authors.lastname: Nakayama
authors.forename: A
authors.initials: A
authors.lastname: Yasuda
authors.forename: A
authors.initials: A
authors.lastname: Matsuda
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry* / Q000494:pharmacology; D007288:Inosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D007893:Leishmania donovani / Q000187:drug effects*; D007895:Leishmania tropica / Q000187:drug effects*; D008325:Mammary Neoplasms, Experimental; D051379:Mice; D015394:Molecular Structure; D009705:Nucleosides / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000981:Antiprotozoal Agents; D009705:Nucleosides; C070277:3'-deoxy-3'-fluoroinosine; D007288:Inosine