Antibacterial activity of griseofulvin analogues as an example of drug repurposing

Antibacterial activity of griseofulvin analogues as an example of drug repurposing Научная публикация

Журнал

International Journal of Antimicrobial Agents
ISSN: 1872-7913 , E-ISSN: 0924-8579

Вых. Данные

Год: 2020, Том: 55, Номер: 3, Номер статьи : 105884, Страниц : DOI: 10.1016/j.ijantimicag.2020.105884

Авторы

Geronikaki A. ¹ , Kartsev V. ² , Petrou A. ¹ , Akrivou M.G. ¹ , Vizirianakis I.S. ¹ , Chatzopoulou F.M. ³ , Lichitsky B. ⁴ , Sirakanyan S. ⁵ , Kostic M. ⁶ , Smiljkovic M. ⁶ , Soković M. ⁷ , Druzhilovskiy D. ⁸ , Poroikov V. ⁸

Организации

1	School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
2	InterBioScreen, Chernogolovka, Moscow, Russia
3	Laboratory of Microbiology, School of Medicine, Faculty of Health Sciencies, Aristotle University of Thessaloniki, Thessaloniki, Greece
4	Zelinsky Institute of Organic Chemistry, Moscow, Russia
5	Scientific Technological Centre of Organic and Pharmaceutical Chemistry of National Academy of Science of Republic of Armenia, Institute of Fine Organic Chemistry of A.L. Mnjoyan, Yerevan, Armenia
6	Mycological Laboratory, Department of Plant Physiology, Institute for Biological Research, Siniša Stanković, University of Belgrade, Belgrade, Serbia
7	Scientific Institute of Veterinary Medicine of Serbia, Belgrade, Serbia
8	Institute of Biomedical Chemistry, Moscow, Russia

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).

Geronikaki A. , Kartsev V. , Petrou A. , Akrivou M.G. , Vizirianakis I.S. , Chatzopoulou F.M. , Lichitsky B. , Sirakanyan S. , Kostic M. , Smiljkovic M. , Soković M. , Druzhilovskiy D. , Poroikov V.
Antibacterial activity of griseofulvin analogues as an example of drug repurposing
International Journal of Antimicrobial Agents. 2020. V.55. N3. 105884 . DOI: 10.1016/j.ijantimicag.2020.105884 WOS Scopus OpenAlex

≡ Web of science:	WOS:000518855500002
≡ Scopus:	2-s2.0-85079833908
≡ OpenAlex:	W3000534229