| Target Validation Information | |||||
|---|---|---|---|---|---|
| TTD ID | T88240 | ||||
| Target Name | Bacterial Dihydropteroate synthetase (Bact folP) | ||||
| Type of Target |
Successful |
||||
| Drug Potency against Target | Dapsone | Drug Info | IC50 = 150 nM | [2] | |
| Daptomycin | Drug Info | MIC90 = 2 ug/ml | [4] | ||
| Sulfadiazine | Drug Info | IC50 = 190 nM | [2] | ||
| Sulfamerazine | Drug Info | IC50 = 78 nM | [2] | ||
| Sulfamethazine | Drug Info | IC50 = 5700 nM | [6] | ||
| Sulfamethizole | Drug Info | IC50 = 7500 nM | [6] | ||
| Sulfamethoxazole | Drug Info | IC50 = 23 nM | [2] | ||
| Sulfapyridine | Drug Info | IC50 = 180 nM | [2] | ||
| Sulfisoxazole | Drug Info | IC50 = 40 nM | [2] | ||
| Sulfonamides | Drug Info | IC50 = 13 nM | [2] | ||
| Sulphadoxine | Drug Info | IC50 = 740 nM | [2] | ||
| Sulphadoxine | Drug Info | IC50 = 740 nM | [2] | ||
| Oritavancin | Drug Info | MIC50 = 0.5 ug/ml | [4] | ||
| 2,6-diamino-5-nitrosopyrimidin-4(3H)-one | Drug Info | IC50 = 8000 nM | [1] | ||
| Action against Disease Model | Dapsone | Drug Info | IC50 for Plasmodi uM falcipar uM isolates from Entosopia, Kenya: 28 ng/mL | [5] | |
| Sulfadiazine | Drug Info | Following 72 h of exposure, the 50% inhibitory concentration of rBPI21 for T. gondii was 2.6 micrograms/ml, whereas only slight cytotoxicity for HFF cells was observed at the concentrations tested. Subsequent mathematical analyses revealed that the combination of rBPI21 with sulfadiazine yielded slight to moderate synergistic effects against T. gondii in vitro. Infection of mice orally with C56 cysts or intraperitoneally (i.p.) with RH tachyzoites resulted in 100% mortality, whereas prolongation of the time to death or significant survival (P = 0.002) was noted for thoseanimals treated with 5 to 20 mg of rBPI21 per kg of body weight per day. Treatment with rBPI21 in combination with sulfadiazine resulted in significant (P = 0.0001) survival of mice infected i.p. with tachyzoites but not of mice infected orally with T. gondii cysts. These results indicate that rBPI21 is active in vitro and in vivo against T. gondii and that its activity is significantly enhanced when it is used in combination with sulfadiazine. | [3] | ||
| References | |||||
| REF 1 | Structural studies of pterin-based inhibitors of dihydropteroate synthase. J Med Chem. 2010 Jan 14;53(1):166-77. | ||||
| REF 2 | Inhibition of recombinant Pneumocystis carinii dihydropteroate synthetase by sulfa drugs. Antimicrob Agents Chemother. 1995 Aug;39(8):1756-63. | ||||
| REF 3 | Recombinant bactericidal/permeability-increasing protein (rBPI21) in combination with sulfadiazine is active against Toxoplasma gondii. Antimicrob Agents Chemother. 1999 Apr;43(4):758-62. | ||||
| REF 4 | Novel antibacterial agents for the treatment of serious Gram-positive infections. Expert Opin Investig Drugs. 2003 Mar;12(3):379-99. | ||||
| REF 5 | Drug susceptibility and genetic evaluation of Plasmodium falciparum isolates obtained in four distinct geographical regions of Kenya. Antimicrob Agents Chemother. 2004 Sep;48(9):3598-601. | ||||
| REF 6 | Interaction of sulfonamide and sulfone compounds with Toxoplasma gondii dihydropteroate synthase. J Clin Invest. 1990 Feb;85(2):371-9. | ||||
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