Pneumocystis carinii synthesis

The main folate antagonist is methotrexate, an analogue of folic acid. Methotrexate competitively inhibits dihydrofolate reductase, the enzyme responsible for the synthesis of purine and pyramidine from folic acid. Trimetrexate, a methotrexate analogue, is useful in treating methotrexate-resistant tumours. It is also used to treat Pneumocystis carinii infections. Methotrexate is usually given orally, but may also be given intravenously or intrathecally. In addition to its use in cancer therapy, it is used in the treatment of psoriasis. Methotrexate can cause an obstructive nephropathy due to its precipitation in the renal calyx. 

Gangjee, A. Guo, X. Queener, S. F. Cody, V. Galitsky, N. Luft, J. R. Pangborn, W. Selective pneumocystis carinii dihydrofolate reductase inhibitors design, synthesis, and biological evaluation of new 2,4-diamino-5-substituted-furo[2,3-d]pyrimidines./. Med. Chem. 1998, 42, 1263-1271. 

Atovaquone is an antiprolozoal agent (750 mg p.o. t.i.d for 21 days), that inhibits mitochondrial electron transport in metabohc enzymes of microorganisms. This may cause inhibition of nucleic acid and adenosine triphosphate synthesis. Atovaquone is indicated in the treatment of mild to moderate Pneumocystis carinii pneumonia in patients who cannot tolerate trimethoprimsulfamethoxazole, and in acute oral treatment of mild to moderate PCP in patients who are intolerant to trimethoprimsulfamethoxazole. 

Rahmathullah, S.M., Hall, J.E., Bender, B.C., et al. (1994) Prodrugs for amidines synthesis and anti-Pneumocystis carinii activity of carbamates of 2,5-bis(4-amidinophenyl)furan. J.Med.Chem. 42 3994-4000. 

Balkovec, J.M., Black, R.M., Hammond, M.L., etal. (1992) Synthesis, stability, and biological evaluation of water-soluble prodrugs of a new echinocandin lipopeptide. Discovery of a potential clinical agent for the treatment of systemic candidiasis and Pneumocystis carinii pneumonia (PCP). J. Med. Chem. 35 194-198. 

A) This combination is effective in the treatment of pneumonia due to Pneumocystis carinii The dmgs produce a sequential blockade of folic acid synthesis Fever and pancytopenia occur frequently when these drugs are used in AIDS patients The combination is appropriate for the treatment of streptococcal pharyngitis The combination is effective in the management of acute exacerbations of chronic bronchitis... 

Co-trimoxazole te.g., Bactrim or Septra) Inhibits the folate synthesis pathway at two different sites (Fig. 7.14). This increases the likelihood that bacteria will produce too little folate to effectively reproduce. Additionally, the likelihood of resistance is substantially reduced. Indicated for urinary tract infections, acute otitis, shigellosis, and Pneumocystis carinii pneumonitis in all age groups. In adults, it is also indicated for exacerbations of chronic bronchitis, bacterial prostatitis and traveller s diarrhea. 

Gangjee, A., Adair, O. and Queener, S. E. 1999. Pneumocystis carinii and Toxoplasma gondii dihydrofolate reductase inhibitors and antitumor agents Synthesis and biological activities of 2,4-diamino-5-methyl-6-[(monosubstitutedanilino)methyl] pyrido[2,3-[Pg.248]

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