02218nas a2200301   4500000000100000008004100001260001200042653001500054653000900069653002500078653001200103653001200115100001100127700001600138700001200154700001200166700001500178700001400193700001100207700001000218700001200228700001500240700001300255245009000268856006100358520148300419022001401902       2021                            d  c06/202110aDNA gyrase10aGyrB10aMycobacterium leprae10aWQ-333410aWQ-38101 aPark J1 aYamaguchi T1 aOuchi Y1 aKoide K1 aPachanon R1 aChizimu J1 aMori S1 aKim H1 aMukai T1 aNakajima C1 aSuzuki Y00aInteraction of Quinolones Carrying New R1 Group with Mycobacterium leprae DNA Gyrase.  uhttps://www.liebertpub.com/doi/pdf/10.1089/mdr.2020.04083 a<p> Leprosy is a chronic infectious disease caused by  and the treatment of choice is ofloxacin (OFX). Specific amino acid substitutions in DNA gyrase of  have been reported leading to resistance against the drug. In our previous study, WQ-3810, a fluoroquinolone with a new R1 group (6-amino-3,5-difluoropyridin-2-yl) was shown to have a strong inhibitory activity on OFX-resistant DNA gyrases of , and the structural characteristics of its R1 group was predicted to enhance the inhibitory activity.  To further understand the contribution of the R1 group, WQ-3334 with the same R1 group as WQ-3810, WQ-4064, and WQ-4065, but with slightly modified R1 group, were assessed on their activities against recombinant DNA gyrase of . An  study was conducted to understand the molecular interactions between DNA gyrase and WQ compounds. WQ-3334 and WQ-3810 were shown to have greater inhibitory activity against  DNA gyrase than others. Furthermore, analysis using quinolone-resistant  DNA gyrases showed that WQ-3334 had greater inhibitory activity than WQ-3810. The R8 group was shown to be a factor for the linkage of the R1 groups with GyrB by an  study.  The inhibitory effect of WQ compounds that have a new R1 group against  DNA gyrase can be enhanced by improving the binding affinity with different R8 group molecules. The information obtained by this work could be applied to design new fluoroquinolones effective for quinolone-resistant  and other bacterial pathogens.</p>  a1931-8448