| Popis: |
This chapter talks about dihydrofolate reductase inhibitors (DHFR), nitroheterocycles (furans), and 8-hydroxyquinolines. Trimethoprim and brodimoprim contain two nitrogen atoms on the pyrimidine ring which are easily protonable according to the pH of environment. Co-trimoxazole is one of the main antibacterial agents for the treatment of uncomplicated cystitis. Pharmacology studies show that the combination of compounds does not modify their behavior and that if co-trimoxazole is compared with the other combinations an advantage may be found for trimethoprim-sulfadiazine in urinary tract infections and renal insufficiency. Many 6-6 fused rings have been prepared with the aim of increasing the selectivity for T. gondii and P. carinii DHFR. A series of hybrids was synthesized. Within this series one analog was 500-fold more potent than trimethoprim against P. carinii and T. gondii and displayed an excellent selectivity. The combination of epiroprim and dapsone is highly effective against P. carinii pneumonia in rats and T. gondii infection in mice. In vitro, the sulfones are active against T. gondii, particularly dapsone. In murine P. carinii pneumocystosis, dapsone is effective in treatment and prevention. In humans, the combination trimethoprim-dapsone in curative treatment and dapsone alone in preventive treatment are effective. Like the sulfonamides, the sulfones interfere with folate synthesis. They also have a potent antioxidant action. Lastly, dapsone inhibits the transport of adenosine through the erythrocyte wall and prevents its incorporation in the nucleic acid of plasmodia and probably toxoplasmas and P. carinii. |
