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- MakaleYalnız künye2020Discovery and evaluation of inhibitory activity and mechanism of arylcoumarin derivatives on Theileria annulata enolase by in vitro and molecular docking studies
Yakarsonmez, Sinem; Danis, Ozkan; Mutlu, Ozal; Topuzogullari, Murat; Sariyer, Emrah; Yuce-Dursun, Basak; Turgut-Balik, Dilek
Abstract: In this study, the inhibition potential of 3- and 4-arylcoumarin derivatives on Theileria annulata enolase (TaENO) was assessed for the first time in the literature. Firstly, protein stabilization analyses of TaENO were performed and it was found that the enzyme remains stable with the addition of 6 M ethylene glycol at + 4 °C. Inhibitor screening analyses were carried out using 25 coumarin derivatives on highly purified TaENO (> 95%), and four coumarin derivatives [4-(3,4-dimethoxyphenyl)-6,7-dihydroxy-2H-chromen-2-one (C8); 4-(3,4-dihydroxyphenyl)-7,8 dihydroxy-2H-chromen-2-one (C9); 4-(3,4-dihydroxyphenyl)-6,7-dihydroxy-2H-chromen-2 one (C21); and 3-(3,4-dihydroxyphenyl)-7,8-dihydroxy-2H-chromen-2-one (C23)] showed the highest inhibitory effects with the IC50 values of 10.450, 13.170, 8.871 and 10.863 µM, respectively. The kinetic results indicated that these compounds inhibited the enzyme by uncompetitive inhibition. In addition, the successful binding of the most potent inhibitor (C21) into TaENO was confirmed by using MALDI-TOF mass spectrophotometry. Molecular docking analyses have predicted that C8 and C21 coumarin derivatives which showed high inhibitory effects on TaENO were interacted with high affinity to the potential regions out of the active site. Taken together, these coumarin derivatives (C8, C9, C21 and C23) are first known potent, nonsubstrate, uncompetitive inhibitors of TaENO and these results will facilitate further in vitro and in vivo analysis toward structure-based drug design studies. Graphic abstract: [Figure not available: see fulltext.]
- MakaleYalnız künye2018Investigation of the inhibitory effects of human carbonic anhydrase i and jack bean urease by coumarin derivates
Aygul, Imdat; Karahalil, Fatma Yaylaci; Danis, Ozkan; Ogan, Ayse; Kolayli, Sevgi
Introduction: This study investigated the in vitro inhibition properties of newly synthesized coumarin derivates (C1-C5) against human carbonic anhdyrase I (hCA-I) and jack bean urease. Activities were expressed as IC50 (mg/mL), the concentration reducing 50% of the enzymes. The IC50 values for hCA-I ranged 5.20 µM from 12.10 µM, with compound C3 exhibiting the highest activity. The inhibition values for urease ranged 22.30 µM to 39.00 µM, the highest activity being observed in C5. Conclusion: Comparing the inhibitions with standard inhibitors of the enzymes, while the samples exhibited moderate inhibitions against hCA I, high inhibition was determined against urease.