Antifolate Resistance Mechanisms from Bacteria to Cancer Cells with Emphasis on Parasites

摘要: Reduced folates serve as co-factors in a variety of one-carbon transfer reactions including the biosynthesis thymidylate, purine nucleotides, and amino acids serine methionine. Dihydrofolate reductase (DHFR) thymidylate synthase (TS) catalyze consecutive de novo synthesis dTMR In protozoa plants, these two enzymes are fused resulting DHFR-TS protein (Ferone Roland, 1980). The enzyme DHFR is target for action antifolates, which widely used during chemotherapeutic interventions. Commonly antifolates shown Figure 1. folate antagonist trimethoprim (TMP) to treat bacterial infections caused by urinary tract or enteric pathogens (Huovinen et al., 1995). antifolate pyrimethamine (PYR) against protozoan parasites Plasmodium Toxoplasma (Borst Ouellette, 1995) whereas trimetrexate with leucovirin fungal Pneumocystis carinii (Hitchings, 1989). methotrexate (MTX) treatment various forms cancer well rheumatoid arthritis, psoriasis some autoimmune diseases (Gorlick 1996). primary structures from organisms share very little homology, hence explaining, part, specificity activity different targeted organisms. basis this selectivity was studied further using comparative enzymology structural analyses. Differences kinetic properties DHFRs likely contribute (Schweitzer 1990).