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Design and synthesis of imidazo[1,2-a]pyridine-chalcone conjugates as antikinetoplastid agents
Agarwal, Devesh S. ; Beteck, Richard M. ; Ilbeigi, Kayhan , et al. Chem. Biol. Drug Des.,2024,103(1):e14400. DOI: 10.1111/cbdd.14400 PubMed ID: 37994272
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Abstract: A library of imidazo[1,2-a]pyridine-appended chalcones were synthesized and characterized using 1H NMR,13C NMR and HRMS. The synthesized analogs were screened for their antikinetoplastid activity against Trypanosoma cruzi, Trypanosoma brucei brucei, Trypanosoma brucei rhodesiense and Leishmania infantum. The analogs were also tested for their cytotoxicity activity against human lung fibroblasts and primary mouse macrophages. Among all screened derivatives, (E)-N-(4-(3-(2-chlorophenyl)acryloyl)phenyl)imidazo[1,2-a]pyridine-2-carboxamide was found to be the most active against T. cruzi and T. b. brucei exhibiting IC50 values of 8.5 and 1.35 μM, resp. Against T. b. rhodesiense, (E)-N-(4-(3-(4-bromophenyl)acryloyl)phenyl)imidazo[1,2-a]pyridine-2-carboxamide was found to be the most active with an IC50 value of 1.13 μM. All synthesized active analogs were found to be non-cytotoxic against MRC-5 and PMM with selectivity indexes of up to more than 50.
Keywords: antikinetoplastid ; chalcone ; drug likeliness properties ; imidazo[1,2-a]pyridine ; neglected tropical diseases (NTDs) ; Trypanosoma brucei brucei ; Trypanosoma brucei rhodesiense
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CAS No. : | 555-16-8 | MDL No. : | MFCD00007346 |
Formula : | C7H5NO3 | Boiling Point : | No data available |
Linear Structure Formula : | C6H4(NO2)(CHO) | InChI Key : | BXRFQSNOROATLV-UHFFFAOYSA-N |
M.W : | 151.12 | Pubchem ID : | 541 |
Synonyms : |
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Signal Word: | Warning | Class: | |
Precautionary Statements: | P501-P273-P264-P280-P337+P313-P305+P351+P338-P302+P352-P332+P313-P362 | UN#: | |
Hazard Statements: | H317-H319-H412 | Packing Group: | |
GHS Pictogram: |
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