Searching for new antimicrobial agents by targeting bacterial nad metabolism: evaluation of frentizole derivatives selected by molecular docking
Abstract
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.