Invention of anti-Leishmania drugs on the basis of the nucleoside structures.
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.
Wataya
Y
Y
Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Tanifuji
H
H
Kubochi
F
F
Yoshioka-Hiramoto
A
A
Morishige
K
K
Ishii
A
A
Morizawa
Y
Y
Nakayama
T
T
Yasuda
A
A
Matsuda
A
A
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
D000981:Antiprotozoal Agents; D009705:Nucleosides; C070277:3'-deoxy-3'-fluoroinosine; D007288:Inosine