Design, Synthesis and Evaluation of Trisubstituted Thiazoles Targeting Plasmodium Falciparum Cysteine Proteases
| Autor: | Babu L. Tekwani, P. Mallikarjun Goud, Prashant V. Desai, Yogesh A. Sabnis, Philip J. Rosenthal, Anjaneyulu Sheri, Jiri Gut, E. Blake Watkins, Mitchell A. Avery |
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| Rok vydání: | 2005 |
| Předmět: |
chemistry.chemical_classification
Proteases biology Stereochemistry Organic Chemistry Plasmodium falciparum biology.organism_classification Formylation chemistry.chemical_compound Enzyme chemistry Biochemistry Wittig reaction Sandmeyer reaction General Pharmacology Toxicology and Pharmaceutics Thiazole Cysteine |
| Zdroj: | Medicinal Chemistry Research. 14:74-105 |
| ISSN: | 1554-8120 1054-2523 |
| DOI: | 10.1007/s00044-005-0126-y |
| Popis: | The Plasmodium falciparum cysteine proteases, falcipains, have been established as novel targets for antimalarial drug design. Using the de novo design approach, several trisubstituted thiazole analogs were generated as potential inhibitors of these enzymes. A general and convenient synthetic approach for these novel trisubstituted thiazoles is reported here. Substituents at the 4th and 5th positions of the target thiazoles were introduced by a Hantzsch reaction, and the chain at the second position was extended through a Sandmeyer reaction, formylation, and Wittig olefination. In vitro enzyme inhibition studies have identified three inhibitors (14, 16, 23) of the falcipains with one (14) showing dual activity against both falcipain-2 and falcipain-3 and IC50 values of 6.6 and 29.4 μM, respectively. |
| Databáze: | OpenAIRE |
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