ABSTRACT
Trypanothione reductase (TR) catalyzes the NAPDH-dependent reduction of the spermidine-glutathione conjugate trypanothione, an antioxidant found in Trypanosomatid parasites. TR plays an essential role in the parasite's defense against oxidative stress and has emerged as a prime target for drug development. Here we report the synthesis of several trypanothione analogues and their inhibitory effects on T. cruzi TR. All are competitive inhibitors with K(i) values ranging from 30 to 91 microM.
Subject(s)
Enzyme Inhibitors/chemical synthesis , NADH, NADPH Oxidoreductases/antagonists & inhibitors , Trypanosoma/enzymology , Animals , Enzyme Inhibitors/chemistry , Glutathione Reductase/chemistry , Indicators and Reagents , NADH, NADPH Oxidoreductases/chemistry , NADP/chemistry , Substrate SpecificityABSTRACT
To assess whether dipyridamole was being used appropriately in providing antiplatelet therapy at the San Diego VAMC, a drug utilization review was conducted. Concomitant aspirin therapy was required for dipyridamole to be considered effective in the disease states reviewed. Seventy-three patients on antiplatelet therapy were evaluated, using dosing criteria established through a literature review. Our data indicated tht based on the criteria, only 11% of patients received dipyridamole in appropriate doses; it was underdosed in 89% of patients, and in 19% of patients, it was used when not indicated. In addition, 19% of patients did not receive concomitant aspirin therapy. Results suggest hat dipyridamole is not used optimally in providing antiplatelet therapy to patients in this institution.
