Comparative effects of 4-aminopyrazolopyrimidine, its 2'-deoxyriboside derivative, and allopurinol on in vitro growth of American Leishmania species.

Antimicrobial Agents and Chemotherapy
J L Avila, M A Casanova

Abstract

When assayed on promastigotes of 10 American Leishmania isolates (including Leishmania brasiliensis and mexicana species), 4-aminopyrazolopyrimidine (AAP) was severalfold more active than allopurinol as a leishmanistatic drug. There were some intraspecific and interspecific differences among the isolates in their susceptibility to the inhibitory effects of APP and allopurinol. APP-2'-deoxyriboside did not affect the 10 isolates tested. This was surprising, because allopurinol riboside has previously been shown to be more active than allopurinol. In all of the American Leishmania isolates tested, the metabolism of [14C]6-APP resulted in a high level of HPP-ribose-5'-P and lower levels of APP-ribose-5'-P, APP-ribose-5'-PP, and APP-ribose-5'-PPP. MP, LR, LBY, and JAP isolates strongly converted APP into APP derivatives, thus perhaps explaining their greater susceptibility to the inhibitory effects of APP. With the 10 American Leishmania isolates tested, several purines reversed the inhibitory effects of allopurinol, but only adenine countered the inhibitory effects of APP. This suggests biochemical differences in the mechanisms of action of allopurinol and APP. Finally, and contrary to previous claims, the reversal by purines of t...Continue Reading

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Citations

Jan 1, 1985·Comparative Biochemistry and Physiology. B, Comparative Biochemistry·C Nosei, J L Avila
Jan 1, 1986·Comparative Biochemistry and Physiology. C, Comparative Pharmacology and Toxicology·J L AvilaR K Robins
Jan 1, 1987·Comparative Biochemistry and Physiology. C, Comparative Pharmacology and Toxicology·J L AvilaR K Robins
Jun 12, 2002·Transactions of the Royal Society of Tropical Medicine and Hygiene·Simon L CroftHoward Kendrick
Mar 1, 1987·Antimicrobial Agents and Chemotherapy·J L AvilaR K Robins
Aug 30, 2005·Antimicrobial Agents and Chemotherapy·Mohammed I Al-Salabi, Harry P de Koning
Jan 19, 2006·Clinical Microbiology Reviews·Simon L CroftAlan H Fairlamb
Sep 22, 2007·Acta Tropica·Valdir Sabbaga AmatoAntonio Carlos Nicodemo
Jan 24, 2008·International Journal of Dermatology·Felipe Francisco TuonVicente Amato Neto
Nov 13, 2001·Tropical Medicine & International Health : TM & IH·S L Croft
Oct 27, 2005·Nucleosides, Nucleotides & Nucleic Acids·K N TiwariJ A Secrist
Mar 31, 2021·Journal of Medicinal Chemistry·Jakob BoutonSerge Van Calenbergh
Jan 1, 1984·Infection and Immunity·J L AvilaM Rieber

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