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Inosine Analogs as Anti-Leishmanial Agents |
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| Authors: | Rainey Petrie Nolan Patricia A Townsend Leroy B Robins Roland K Fox Jack J Secrist III John A Santi Daniel V |
| Institution: | (1) Department of Laboratory Medicine, School of Medicine, University of California, San Francisco, CA 94143, USA;(2) Department of Biochemistry and Biophysics and Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143, USA;(3) Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA;(4) Cancer Research Center, Department of Chemistry, Brigham Young University, Provo, UT 84602, USA;(5) Laboratory of Organic Chemistry, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA;(6) Southern Research Institute, P.O. Box 55305, Birmingham, Alabama 35255, USA |
| Abstract: | Several criteria were used to select a number of inosine analogs as potential growth inhibitors of the protozoan parasite Leishmania tropica. Of nine compounds tested, seven showed a high degree of selective toxicity towards L. tropica promastigotes as compared to mouse L1210 cells; these include analogs of formycin B, 7-substituted analogs of 7-deazainosine and analogs of inosine in which the sugar moiety has been modified to confer metabolic stability. The metabolism of 7-deazainosine in L. tropica promastigotes was shown to involve conversion to cytotoxic adenosine nucleotide analogs (tubercidin derivatives) that become incorporated into RNA. The results suggest several new classes of compounds which have potential as anti-leishmanial agents. |
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