Development of new antimycobacterial agents for Mycobacterium avium complex (MAC) infections is important particularly for persons coinfected with human immunodeficiency virus. The objectives of this study were to evaluate the in vitro activity of 2, 4-diamino-5-methyl-5-deazapteridines (DMDPs) against MAC and to assess their activities against MAC dihydrofolate reductase recombinant enzyme (rD...

From a mutagenized population of wild type Leishmania donovani promastigotes, a clone was isolated in a single step by virtue of its resistance to 1 mM methotrexate, a potent inhibitor of dihydrofolate reductase. This methotrexate-selected cell line, MTXA5, was cross-resistant to aminopterin but just as sensitive to growth inhibition caused by pyrimethamine, trimethoprim, and cytotoxic purine a...

The enzymatic synthesis of dihydropteroate or dihydrofolate from 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine and p-aminobenaoate or p-aminobenzoylglutamate by bacterial extracts has been shown to require adenosine triphosphate (I-3). It has been postulated that a phosphorylated pteridine intermediate is involved before synthesis of folate-like compounds. Jaenicke and Chan (4) reported tha...

In order to continue our studies in coordination chemistry with pteridine derivatives, four new complexes with general formula MX2(pteridine)2 /nH2O /mCH3CN (M /Cu, Pd, Pt) have been synthesized by reaction of 1-methyllumazine (MLM) and 1,6,7trimethyllumazine (MLMD) and different halide salts in acetonitrile solutions. These compounds have been characterized by means of analytical techniques (e...

INTRODUCTION As well as folate (a conjugated pteridine) in plants and microorganisms, tetrahydrobiopterin (BH4, an unconjugated pteridine) in animals is also biosynthesized from GTP. So far three essential enzymes have been identified as being active in BH4 synthesis[1,2], while only the initial enzyme of the pathway is common with that of the folate pathway (Fig. 1). Since the cell level of BH...

Physarum polycephalum, an acellular slime mould, serves as a model system to study cell-cycle-dependent events since nuclear division is naturally synchronous. This organism was shown to release isoxanthopterin which is structurally related to tetrahydrobiopterin, a cofactor of aromatic amino acid hydroxylases and of nitric oxide synthases (NOSs) (EC 1.14.13.39). Here, we studied Physarum pteri...

Nonribosomal peptides represent a large class of metabolites with pharmaceutical relevance. Pteridines, such as pterins, folates, and flavins, are heterocyclic metabolites that often serve as redox-active cofactors. The biosynthetic machineries for construction of these distinct classes of small molecules operate independently in the cell. Here, we discovered an unprecedented nonribosomal pepti...

Leishmania parasites possess an abundance of ether-linked hydrocarbons as components of phospholipids and glycosylphosphatidylinositol anchors of glycoproteins and polysaccharides, including important surface molecules such as lipophosphoglycan (LPG) and glycosylinositolphospholipids (GIPLs). Cleavage of the ether bond is an important feature in the turnover pathway of alkylglycerols. In mammal...