Lead derivatization of ethyl 6-bromo-2-((dimethylamino)methyl)-5-hydroxy-1-phenyl-1H-indole-3-carboxylate and 5-bromo-2-(thiophene-2-carboxamido) benzoic acid as FabG inhibitors targeting ESKAPE pathogens
| Autor: | Robert Schnell, Sriram Dharmarajan, Saiprasad Dasugari Varakala, Rudraraju Srilakshmi Reshma |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
Pharmacology
chemistry.chemical_classification Indole test Dose-Response Relationship Drug Molecular Structure Stereochemistry Organic Chemistry Allosteric regulation Fatty acid Microbial Sensitivity Tests General Medicine Anti-Bacterial Agents Structure-Activity Relationship chemistry.chemical_compound chemistry Pseudomonas Drug Discovery Thiophene Carboxylate Enzyme Inhibitors Oxidoreductases Derivatization Lead compound Benzoic acid |
| Zdroj: | European Journal of Medicinal Chemistry. 228:113976 |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2021.113976 |
| Popis: | Our previous studies on FabG have identified two compounds 5-bromo-2-(thiophene-2-carboxamido) benzoic acid (A) and ethyl 6-bromo-2-((dimethylamino)methyl)-5-hydroxy-1-phenyl-1H-indole-3-carboxylate(B) as best hits with allosteric mode of inhibition. FabG is an integral part of bacterial fatty acid biosynthetic system FAS II shown to be an essential gene in most ESKAPE Pathogens. The current work is focussed on lead expansion of these two hit molecules which ended up with forty-three analogues (twenty-nine analogues from lead compound A and fourteen compounds from lead compound B). The enzyme inhibition studies revealed that compound 15 (effective against EcFabG, AbFabG, StFabG, MtFabG1) and 19 (inhibiting EcFabG and StFabG) had potency of broad-spectrum inhibition on FabG panel. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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