In:
Eukaryotic Cell, American Society for Microbiology, Vol. 8, No. 4 ( 2009-04), p. 483-486
Abstract:
Trimethoprim, an antifolate commonly prescribed in combination with sulfamethoxazole, potently inhibits several prokaryotic species of dihydrofolate reductase (DHFR). However, several eukaryotic pathogenic organisms are resistant to trimethoprim, preventing its effective use as a therapeutic for those infections. We have been building a program to reengineer trimethoprim to more potently and selectively inhibit eukaryotic species of DHFR as a viable strategy for new drug discovery targeting several opportunistic pathogens. We have developed a series of compounds that exhibit potent and selective inhibition of DHFR from the parasitic protozoa Cryptosporidium and Toxoplasma as well as the fungus Candida glabrata . A comparison of the structures of DHFR from the fungal species Candida glabrata and Pneumocystis suggests that the compounds may also potently inhibit Pneumocystis DHFR.
Type of Medium:
Online Resource
ISSN:
1535-9778
,
1535-9786
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2009
detail.hit.zdb_id:
2071564-X
SSG:
12
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