From: In silico work flow for scaffold hopping in Leishmania
No. | PROTEIN | Inhibitor name | IC50 /Ki |
---|---|---|---|
i1 | Pteridine Reductase 1 | methotrexate (nature structural biology, volume 8, number 6, june 2001) | 1.1 μM |
i2 | Pteridine Reductase 1 | Trimethoprim (Experimental Parasitology 87, 157–169 (1997)) | 12 μM |
i3 | Pteridine Reductase 1 | 10 – propargyl-5,8-dideazafolic acid (J. Mol. Biol. (2005) 352, 105–116) | > 10 μM |
i4 | Trypanothione Reductase | methyl [(4S) - 6 - bromo - 2 - methyl - 4 - phenylquinazolin - 3(4H)-YL] acetate (J. Med. Chem. 2011, 54, 6514–6530) | 6.8 μM |
i5 | Trypanothione Reductase | (4 s) - 3 - benzyl - 6 - chloro - 2 - methyl - 4 - phenyl - 3,4 – dihydroquinazoline (J. Med. Chem. 2011, 54, 6514–6530) | 0.93 μM |
i6 | Trypanothione Reductase | n - {2 - [(4 s) - 6 - chloro - 2 - methyl - 4 - phenylquinazolin - 3(4 h) - yl] ethyl}furan - 2 – carboxamide (J. Med. Chem. 2011, 54, 6514–6530) | 0.86 μM |
i7 | Trypanothione Reductase | (4 s) - 6 - chloro - 3 - {2 - [4 - (furan - 2 - ylcarbonyl)piperazin - 1 - yl]ethyl} -2 - methyl - 4 - phenyl - 3,4 –dihydroquinazoline (J. Med. Chem. 2011, 54, 6514–6530) | 0.42 μM |
i8 | Trypanothione Reductase | 3 - [(4 s) - 6 - chloro - 2 - methyl - 4 - (4 - methylphenyl) quinazolin - 3(4 h) -yl] - n,n - dimethylpropan - 1 – amine (J. Med. Chem. 2011, 54, 6514–6530) | 0.23 μM |
i9 | Trypanothione Reductase | a C6 - substituted and C8 - substituted 3,4 - dihydroquinazoline analogue (J. Med. Chem. 2011, 54, 6514–6530) | 0.35 μM |
i10 | Pteridine Reductase 1 | a quinazoline derivative (Experimental Parasitology 1997, 87, 157–169 ) | 0.4 μM |
i11 | Pteridine Reductase 1 | a 2,4-Diaminopyrimidine derivative (Experimental Parasitology 1997 ,87, 157–169 ) | 0.4 μM |
iTb4 to iTb8 | Trypanothione Reductase crystal complex from T. brucei | Above inhibitor i1 to i5. (J. Med. Chem. 2011, 54, 6514–6530) | Same as above |
i12 | ATP dependent Phospho Fructo Kinase | a N, N0 - substituted - 1-amino - 2, 5 - anhydro - 1 - deoxy - 1 - D -mannonamide derivatives (Bioorg. Med. Chem. 2008, 16 , 5050–5061) | 49 μM |
i13 | ATP dependent Phospho Fructo Kinase | 2, 5 - anhydro - 1 - deoxy - 1 - (3, 4 - dichlorobenzylamino) - D – mannitol (Bioorg. Med. Chem. 2008, 16 , 5050–5061) | 0.4 μM |
i14 | ATP dependent Phospho Fructo Kinase | 2, 5 - Anhydro - 1 - deoxy - 1 - (3, 4 - dichlorobenzylamino) - D - 3, 4 - dichlorobenzylmannonamide (Bioorg. Med. Chem. 2008, 16 , 5050–5061) | 23 μM |
i15 | Deoxyuridine Triphosphate Nucleotidohydrolase | a 5′ - tert - butyldiphenylsilyloxy derivative (J. Med. Chem. 2005, 48, 5942–5954) | 3.0 μM |
i16 | Deoxyuridine Triphosphate Nucleotidohydrolase | a 5′ - Ph3CNH derivative (J. Med. Chem. 2005, 48, 5942–5954) | NA; substrate analog |
i17 | Deoxyuridine Triphosphate Nucleotidohydrolase | 5′ - tritylamino - 3′ - fluoro - 2′, 3′, 5′ – trideoxyuridine (J. Med. Chem. 2005, 48, 5942–5954) | 3.6 μM |
i18 | Deoxyuridine Triphosphate Nucleotidohydrolase | 5′ - O - triphenylsilyl - 2′, 3′ - didehydro - 2′, 3′ – dideoxyuridine (J. Med. Chem. 2005, 48, 5942–5954) | 12 μM |
i19 | Nonspecific Nucleoside Hydrolase | immucillin A (J. Biol. Chem. 1999,274(30, 21114–21120) | 15 nM |
i20 | Nonspecific Nucleoside Hydrolase | immucilin ACAP (J. Biol. Chem.1999, 274(30), 21114–21120) | 6.5 nM |
i21 | Nonspecific Nucleoside Hydrolase | N - (9 - deaza - adenin - 9 - yl) methyl - 1, 4 - dideoxy - 1, 4 - imino - D - ribitol (Antimicrobial Agents and Chemotherapy, 2010, 1900–1908) | 0.49 μM |
i22 | Nonspecific Nucleoside Hydrolase | immucillin-H (1, 4 - dideoxy - 4 - aza - 1 - (s) - (9 - deazahypoxanthin - 9 - yl) - d - ribitol) (Biochem Biophys. Acta.2009, 1794, 953–960) | Ki = 6.2 nM |
i23 | Nonspecific Nucleoside Hydrolase | 7 - (((2R, 3R, 4S) - 3, 4 - dihydroxy - 2 - (hydroxymethyl) pyrrolidin - 1 - yl) methyl) - 3H - pyrrolo [3, 2-d] pyrimidin - 4 (5H) - one (Biochem Biophys. Acta. 2009, 1794 , 953–960) | Ki = 4.4 nM |
i24 | Nonspecific Nucleoside Hydrolase | (2R, 3R, 4S) - 2 - (hydroxymethyl) - 1 - (quinolin - 8 - ylmethyl) pyrrolidine - 3, 4 – diol (Biochem Biophys. Acta. 2009, 1794, 953–960) | Ki = 10.8 μM |
i25 | Trypanothione Synthetase | 1-[3-(3-fluorophenyl)indazol-1-yl]-3,3-dimethylbutan-2-one (J.Biol.Chem., 2009, 284( 52), pp. 36137–36145) | 0.095 μM |
i26 | Putative-UDP-glc-4′-epimerase | ebselen (Bioorg. & Med. Chem. Lett. 2006, 16 , 5744–5747) | 0.62 μM |
i27 | GLO1 | S-4-bromobenzylglutathionylspermidine (Molecular Microbiology,2006, 59, 1239–1248) | Ki = 0.54 μM |