Antibacterial azole derivatives: Antibacterial activity, cytotoxicity, and in silico mechanistic studies
| Autor: | İrem Bozbey, İnci Selin Doğan, Ebru Koçak, Didem Kart, Zeynep Özdemir, Ahmet Avci, Suat Sari, Suna Sabuncuoğlu, Sevim Dalkara, Selma Saraç, Arzu Karakurt |
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| Rok vydání: | 2020 |
| Předmět: |
chemistry.chemical_classification
Econazole biology Chemistry Broth microdilution Pharmacology biology.organism_classification Enterococcus faecalis 3. Good health 03 medical and health sciences Minimum inhibitory concentration 0302 clinical medicine Docking (molecular) 030220 oncology & carcinogenesis Drug Discovery medicine Azole Miconazole Antibacterial activity 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Drug Development Research. 81:1026-1036 |
| ISSN: | 1098-2299 0272-4391 |
| DOI: | 10.1002/ddr.21721 |
| Popis: | Azole antifungal drugs are commonly used in antifungal chemotherapy. Antibacterial effects of some topical antifungals, such as miconazole and econazole, have lately been revealed, which suggests a promising venue in antimicrobial chemotherapy. In this study, we tested an in-house azole collection with antifungal properties for their antibacterial activity to identify dual-acting hits using the broth microdilution method. The in vitro screen yielded a number of potent derivatives against gram-positive bacteria, Enterococcus faecalis and Staphylococcus aureus. Compound 73's minimum inhibitory concentration (MIC) value less than 1 μg/ml against S. aureus; however, none of the compounds showed noteworthy activity against methicillin-resistant S. aureus (MRSA). All the active compounds were found safe at their MIC values against the healthy fibroblast cells in the in vitro cytotoxicity test. Molecular docking studies of the most active compounds using a set of docking programs with flavohemoglobin (flavoHb) structure, the proposed target of the azole antifungals with antibacterial activity, presented striking similarities regarding the binding modes and interactions between the tested compounds and the antifungal drugs with crystallographic data. In addition to being noncytotoxic, the library was predicted to be drug-like and free of pan-assay interference compounds (PAINS). As a result, the current study revealed several potential azole derivatives with both antifungal and antibacterial activities. Inhibition of bacterial flavoHb was suggested as a possible mechanism of action for the title compounds. |
| Databáze: | OpenAIRE |
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