Bioorganic & medicinal chemistry, 2012-02, Vol.20 (3), p.1240-1250
2012
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- Autor(en) / Beteiligte
- Titel
- Identification of Trypanosoma brucei leucyl-tRNA synthetase inhibitors by pharmacophore- and docking-based virtual screening and synthesis
- Ist Teil von
- Bioorganic & medicinal chemistry, 2012-02, Vol.20 (3), p.1240-1250
- Ort / Verlag
- Amsterdam: Elsevier Ltd
- Erscheinungsjahr
- 2012
- Quelle
- Access via ScienceDirect (Elsevier)
- Beschreibungen/Notizen
- Human African trypanosomiasis (HAT), caused by the protozoan parasite Trypanosoma brucei, is a neglected fatal disease. Leucyl-tRNA synthetase (LeuRS), which has been successfully applied in the development of antifungal agent, represents a potential antiprotozoal drug target. In this study, a 3D model of T. brucei LeuRS (TbLeuRS) synthetic active site was constructed and subjected to virtual screening using a combination of pharmacophore- and docking-based methods. A new 2-pyrrolinone scaffold was discovered and the structure–activity relationship (SAR) studies aided by the docking model and organic synthesis were carried out. Compounds with various substituents on R1, R2 and R3 were synthesized and their SAR was discussed.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0968-0896eISSN: 1464-3391DOI: 10.1016/j.bmc.2011.12.035Titel-ID: cdi_proquest_miscellaneous_923209569
- Format
- –
- Schlagworte
- active sites, African trypanosomiasis, Amino Acid Sequence, Antifungal agents, Antiprotozoal Agents - chemical synthesis, Antiprotozoal Agents - chemistry, Antiprotozoal Agents - pharmacology, Biological and medical sciences, Catalytic Domain, Docking, Drug Design, Drug development, drugs, Human African trypanosomiasis, Humans, Leucine-tRNA ligase, Leucine-tRNA Ligase - antagonists & inhibitors, Leucine-tRNA Ligase - chemistry, Leucine-tRNA Ligase - metabolism, Leucyl-tRNA synthetase, Medical sciences, Models, Molecular, Molecular Sequence Data, Parasites, Pharmacology. Drug treatments, Pharmacophore, scaffolds, screening, Sequence Alignment, Structure-Activity Relationship, Structure-activity relationships, Trypanosoma brucei, Trypanosoma brucei brucei - drug effects, Trypanosoma brucei brucei - enzymology, Trypanosomiasis, African - drug therapy, Trypanosomiasis, African - enzymology, Virtual screening