Synthesis and mycobacterial evaluation of 5‐substituted‐6‐acetyl‐2‐amino‐7‐methyl‐5,8‐dihydropyrido‐[2,3‐d]pyrimidin‐4(3H)‐one derivatives
| Autor: | Sanjib Bhakta, Neha Agre, Mukti Kanta Ray, Antima Gupta, Mariam S. Degani |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Staphylococcus aureus
Cell Survival THP-1 Cells Antitubercular Agents Pharmaceutical Science Microbial Sensitivity Tests medicine.disease_cause 01 natural sciences Mycobacterium aurum Mice Structure-Activity Relationship Minimum inhibitory concentration Drug Discovery Escherichia coli medicine Animals Humans Cytotoxic T cell Cytotoxicity Mycobacteriaceae Molecular Structure biology 010405 organic chemistry Chemistry Mycobacterium tuberculosis biology.organism_classification Molecular biology Anti-Bacterial Agents 0104 chemical sciences 010404 medicinal & biomolecular chemistry Pyrimidines RAW 264.7 Cells Cell culture Drug Design Efflux |
| Zdroj: | Archiv der Pharmazie. 352:1900068 |
| ISSN: | 1521-4184 0365-6233 |
| Popis: | 5-Substituted-6-acetyl-2-amino-7-methyl-5,8-dihydropyrido[2,3-d]pyrimidin-4(3H)-one derivatives were synthesized and evaluated against Mycobacterium tuberculosis H37Rv, Mycobacterium aurum, Escherichia coli, and Staphylococcus aureus as well as a human monocyte-derived macrophage (THP-1), and murine macrophage (RAW 264.7) cell lines to assess their antibacterial and cytotoxic potential, respectively. The compounds showed activity in the range of 1.95-125 µg/ml against M. tuberculosis but showed no activity against M. aurum, E. coli, and S. aureus, indicating selectivity towards slow-growing mycobacterial pathogens. The compounds exhibited very low to no cytotoxicity up to 500 µg/ml concentration against eukaryotic cell lines. The most potent molecule, 2l, showed a minimum inhibitory concentration of 1.95 µg/ml against M. tuberculosis H37Rv and a selectivity index of >250 against both the eukaryotic cell lines. Furthermore, 2l showed moderate inhibition of whole-cell mycobacterial drug-efflux pumps when compared to verapamil, a known potent inhibitor of efflux pumps. Thus, derivative 2l was identified as an antituberculosis hit molecule, which could be used to yield more potent lead molecules. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text