Novel anti-tubercular and antibacterial based benzosuberone-thiazole moieties: Synthesis, molecular docking analysis, DNA gyrase supercoiling and ATPase activity
| Autor: | Marwa M. Abdel-Aziz, Thoraya A. Farghaly, Ghada S. Masaret, Marwa F. Harras, Mohamed A. Omar, Eman M. H. Abbas |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Microbial Sensitivity Tests
ATPase binding 01 natural sciences Biochemistry DNA gyrase Bordetella pertussis Cell Line Structure-Activity Relationship chemistry.chemical_compound Coumarins Drug Discovery medicine Humans Topoisomerase II Inhibitors Thiazole Molecular Biology Adenosine Triphosphatases Dose-Response Relationship Drug Molecular Structure biology 010405 organic chemistry Organic Chemistry Isoniazid Mycobacterium tuberculosis biology.organism_classification Anti-Bacterial Agents Mycoplasma pneumoniae 0104 chemical sciences Molecular Docking Simulation Ciprofloxacin Thiazoles 010404 medicinal & biomolecular chemistry chemistry DNA Gyrase DNA supercoil Bacteria DNA medicine.drug |
| Zdroj: | Bioorganic Chemistry. 104:104316 |
| ISSN: | 0045-2068 |
| DOI: | 10.1016/j.bioorg.2020.104316 |
| Popis: | Herein, molecular hybridization strategy was utilized in the design of new benzosuberone-thiazole derivatives. The structures of the synthesized hybrids were determined on the basis of elemental and spectral analyses. These compounds were evaluated for their antibacterial activities against five bronchitis causing bacteria in addition to their anti-tubercular activities. Most compounds revealed promising activities. Amongst active compounds, benzosuberone-dithiazole derivatives 22a and 28 with MIC value = 1.95 µg/ml against H. influenza, M. pneumonia, and B. pertussis displayed four times the activity of ciprofloxacin (MIC = 7.81 µg/ml) against H. influenza, twice the activity of ciprofloxacin (MIC = 3.9 µg/ml) against M. pneumonia and were equipotent to ciprofloxacin against B. pertussis (MIC = 1.95 µg/ml). Additionally, benzosuberone-dithiazole derivatives 22a and 27 were the most promising anti-tubercular among the tested compounds with MIC values of 0.12 and 0.24 µg/ml, respectively against sensitive M. tuberculosis in addition to high activity against resistant strain of M. tuberculosis (MIC = 0.98 and 1.95 µg/ml, respectively) compared to isoniazid (MIC = 0.12 µg/ml against sensitive M. tuberculosis and no activity against resistant M. tuberculosis). Cytotoxicity study of the active dithiazole derivatives 22a, 27 and 28 against normal human lung cells (WI-38) indicated their high safety profile as showed from their high IC50 values (IC50 = 107, 74.8, and 117 µM, respectively). Furthermore, DNA gyrase supercoiling and ATPase activity assays showed that 22a, 27 and 28 have the potential to inhibit DNA gyrase at low micromolar levels (IC50 = 3.29–15.64 µM). Molecular docking analysis was also carried out to understand the binding profiles of the synthesized compounds into the ATPase binding sites of bacterial and mycobacterial DNA gyraseB. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect