Antibacterial activity of griseofulvin analogues as an example of drug repurposing
•Computational prediction of antibacterial activity.•Similarity assessment.•Antibacterial activity evaluation.•Docking to antibacterial targets. Griseofulvin is a well-known antifungal drug that was launched in 1962 by Merck & Co. for the treatment of dermatophyte infections. However, according...
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| Published in: | International journal of antimicrobial agents Vol. 55; no. 3; p. 105884 |
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| Main Authors: | , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Netherlands
Elsevier B.V
01-03-2020
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| Subjects: | |
| Online Access: | Get full text |
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| Summary: | •Computational prediction of antibacterial activity.•Similarity assessment.•Antibacterial activity evaluation.•Docking to antibacterial targets.
Griseofulvin is a well-known antifungal drug that was launched in 1962 by Merck & Co. for the treatment of dermatophyte infections. However, according to predictions using the Way2Drug computational drug repurposing platform, it may also have antibacterial activity. As no confirmation of this prediction was found in the published literature, this study estimated in-silico antibacterial activity for 42 griseofulvin derivatives. Antibacterial activity was predicted for 33 of the 42 compounds, which led to the conclusion that this activity might be considered as typical for this chemical series. Therefore, experimental testing of antibacterial activity was performed on a panel of Gram-positive and Gram-negative micro-organisms. Antibacterial activity was evaluated using the microdilution method detecting the minimal inhibitory concentration (MIC) and the minimal bactericidal concentration (MBC). The tested compounds exhibited potent antibacterial activity against all the studied bacteria, with MIC and MBC values ranging from 0.0037 to 0.04 mg/mL and from 0.01 to 0.16 mg/mL, respectively. Activity was 2.5–12 times greater than that of ampicillin and 2–8 times greater than that of streptomycin, which were used as the reference drugs. Similarity analysis for all 42 compounds with the (approximately) 470,000 drug-like compounds indexed in the Clarivate Analytics Integrity database confirmed the significant novelty of the antibacterial activity for the compounds from this chemical class. Therefore, this study demonstrated that by using computer-aided prediction of biological activity spectra for a particular chemical series, it is possible to identify typical biological activities which may be used for discovery of new applications (e.g. drug repurposing).
Forty two griseofulvin derivates were evaluated for their antibacterial activity based on the predictions using Way2Drug computational drug repurposing platform, according to which it may have antibacterial activity. Docking studies were perform to find possible mechanism of antibacterial activity. [Display omitted] |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ISSN: | 0924-8579 1872-7913 |
| DOI: | 10.1016/j.ijantimicag.2020.105884 |