Synthesis and DNase I inhibitory properties of some 4-thiazolidinone derivatives |
| |
Authors: | Ana Kolarević Budimir S. Ilić Gordana Kocić Zdravko Džambaski Andrija Šmelcerović Bojan P. Bondžić |
| |
Affiliation: | 1. Department of Pharmacy, Faculty of Medicine, University of Niš, Niš, Serbia;2. Department of Chemistry, Faculty of Medicine, University of Niš, Niš, Serbia;3. Department of Biochemistry, Faculty of Medicine, University of Niš, Niš, Serbia;4. Center for Chemistry ICTM, University of Belgrade, Belgrade, Serbia |
| |
Abstract: | Twelve new thiazolidinones were synthesized and, together with 41 previously synthesized thiazolidinones, evaluated for inhibitory activity against deoxyribonuclease I (DNase I) in vitro. Ten compounds inhibited commercial bovine pancreatic DNase I with an IC50 below 200 μM and showed to be more potent DNase I inhibitors than crystal violet (IC50 = 365.90 ± 47.33 μM), used as a positive control. Moreover, three compounds were active against DNase I in rat liver homogenate, having an IC50 below 200 μM. (3-Methyl-1,4-dioxothiazolidin-2-ylidene)-N-(2-phenylethyl)ethanamide ( 41 ) exhibited the most potent DNase I inhibition against both commercial and rat liver DNase I with IC50 values of 115.96 ± 11.70 and 151.36 ± 15.85 μM, respectively. Site Finder and molecular docking defined the thiazolidinones interactions with the most important catalytic residues of DNase I, including the H-acceptor interaction with residues His 134 and His 252 and/or H-donor interaction with residues Glu 39 and Asp 168. The three most active compounds against both commercial and rat liver DNase I ( 31 , 38 , and 41 ) exhibited favorable physico-chemical, pharmacokinetic, and toxicological properties. These observations could be utilized to guide the rational design and optimization of novel thiazolidinone inhibitors. Thiazolidinones as novel DNase I inhibitors could have potential therapeutic applications due to the significant involvement of DNase I in the pathophysiology of many disease conditions. |
| |
Keywords: | DNase I inhibition molecular docking synthesis thiazolidinones |
|
|