Antileishmanial activity of inosine analogs on promastigote forms of Iraqi Leishmanial species

Abstract

A B S T R A C TThe growth inhibitory effects of inosine analogs, allopurinol, thiopurinol, allopurinol riboside, formycin B, thioformycin B, 7-deazainosine, 9-deazainosine, 8-azainosine and thio-7-deazainosine were tested against promastigotes of Leishmania tropica, L.major and L.donovani. All ten analogs were active against all the three species. The efficacy and metabolism of the formycin B, allopurinol riboside, 7-deazainosine and 9-deazainosine in leishmanial species were evaluated. These analogs affect several metabolic processes. First, is the increased catabolism of RNA and consequent reduction of protein synthesis. Second, inhibition of adenosine kinase, adenylosuccinate synthetase and adenylosuccinate lyase which reduces the organisms ability to synthesize ATP. Third, inhibition of IMP dehydrogenase and GMP reductase ought to be sufficient to half the interconversion of adenine nucleotides to guanine nucleotides and vice versa. The results suggests that such inosine analogs may have promise as antileishmanial agents.