9HUU
Trypanosoma brucei PTR1 (TbPTR1) in complex with inhibitor F223
This is a non-PDB format compatible entry.
Summary for 9HUU
| Entry DOI | 10.2210/pdb9huu/pdb |
| Related | 9HUP 9HUT |
| Descriptor | Pteridine reductase, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, 2-azanyl-~{N}-[2-(4-chlorophenyl)ethyl]-1,3-benzothiazole-6-carboxamide, ... (7 entities in total) |
| Functional Keywords | trypanosoma brucei, pteridine reductase, ptr1, tbptr1, benzothiazole, oxidoreductase |
| Biological source | Trypanosoma brucei brucei |
| Total number of polymer chains | 4 |
| Total formula weight | 127525.77 |
| Authors | |
| Primary citation | Panecka-Hofman, J.,Linciano, P.,Pohner, I.,Dyguda-Kazimierowicz, E.,Jedwabny, W.,Landi, G.,Santarem, N.,Witt, G.,Ellinger, B.,Kuzikov, M.,Luciani, R.,Ferrari, S.,Aiello, D.,Mangani, S.,Pozzi, C.,Cordeiro-da-Silva, A.,Gul, S.,Costi, M.P.,Wade, R.C. Design of 2-Aminobenzothiazole Derivatives Targeting Trypanosomatid PTR1 by a Multidisciplinary Fragment Hybridization Approach. J.Med.Chem., 68:20595-20618, 2025 Cited by PubMed Abstract: Pteridine reductase 1 (PTR1) is a folate pathway enzyme essential for pathogenic trypanosomatids and a promising drug target for diseases such as sleeping sickness and leishmaniasis. Previous studies have shown that the 2-aminobenzothiazole moiety targets the PTR1 biopterin pocket, while 3,4-dichlorophenyl-containing compounds, such as bind a different region of the PTR1 (PTR1) pocket. This study combines both moieties via various linkers, creating two compound series screened in silico against PTR1 and PTR1 (PTR1). In the first series, five compounds were synthesized, and and emerged as potent PTR1 inhibitors, with also being active against PTR1 and moderately effective against . Furthermore, structure-activity relationship analysis, supported by quantum calculations and crystallography, revealed meta-halogenation to be more favorable than para, although single halogenation reduced antiparasite effects. Our fragment hybridization approach led to less toxic, more effective compounds than . PubMed: 41026998DOI: 10.1021/acs.jmedchem.5c01799 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.85 Å) |
Structure validation
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