MMSL 2020, 89(2):66-73 | DOI: 10.31482/mmsl.2020.005

SEARCHING FOR NEW ANTIMICROBIAL AGENTS BY TARGETING BACTERIAL NAD METABOLISM: EVALUATION OF FRENTIZOLE DERIVATIVES SELECTED BY MOLECULAR DOCKINGOriginal article

Michaela Hympanova ORCID...1,3, Tomas Kucera ORCID...1, Ondrej Benek ORCID...2, Jan Korabecny ORCID...1,3*, Jan Marek ORCID...1,3*
1 Department of Epidemiology, Department of Toxicology and Military Pharmacy; Faculty of Military Health Sciences, University of Defence in Brno, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic
2 Department of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanskeho 62, 500 03 Hradec Kralove, Czech Republic
3 Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic

Growing evidence of antibiotic-resistant pathogens is a serious medical issue that has to be addressed. Our antimicrobial research is focused on searching for novel small molecules that differ from the most clinically used antibiotics by chemical structure and mechanism. However, this fundamental research is like looking for a needle in a haystack. In addition, in vitro methods are time-consuming and expensive to screen large number of compounds in reasonable time. Off-target screening can represent a solution to find novel and effective antimicrobial agents that can eliminate these problems. Accordingly, molecular docking in the family of selected frentizole derivatives predicted their potential to inhibit bacterial nicotinate mononucleotide adenylyltransferase (NadD). This bacterial-essential specific enzyme has an important role in NAD metabolism. Thus, underlying mechanism of antimicrobials derived from frentizole would be interference with this biochemical process. Unfortunately, broth microdilution assay did not display any antimicrobial activity of tested compounds. On the other hand, herein we propose that off-target screening can facilitate searching for new drugs and that NadD could be a relevant target for antimicrobials.

Keywords: antimicrobials; molecular docking; NadD inhibitors; frentizole derivatives

Received: January 21, 2020; Revised: February 25, 2020; Accepted: February 25, 2020; Prepublished online: March 13, 2020; Published: June 5, 2020  Show citation

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Hympanova, M., Kucera, T., Benek, O., Korabecny, J., & Marek, J. (2020). SEARCHING FOR NEW ANTIMICROBIAL AGENTS BY TARGETING BACTERIAL NAD METABOLISM: EVALUATION OF FRENTIZOLE DERIVATIVES SELECTED BY MOLECULAR DOCKING. MMSL, 89(2), 66-73. doi: 10.31482/mmsl.2020.005
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