Deoxyribonuclease I Inhibitory Properties,Molecular Docking and Molecular Dynamics Simulations of 1-(Pyrrolidin-2-yl)propan-2-one Derivatives |
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| Authors: | Budimir S. Ilić Mihajlo Gajić Bojan P. Bondžić Zdravko Džambaski Gordana Kocić Andrija Šmelcerović |
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| Affiliation: | 1. University of Niš, Faculty of Medicine, Department of Chemistry, Blvd. Dr. Zorana Đinđića 81, 18000 Niš, Serbia;2. University of Niš, Faculty of Medicine, Department of Pharmacy, Blvd. Dr. Zorana Đinđića 81, 18000 Niš, Serbia;3. University of Belgrade, Institute of Chemistry, Technology and Metallurgy, Njegoševa 12, 11000 Belgrade, Serbia;4. University of Niš, Faculty of Medicine, Department of Biochemistry, Blvd. Dr. Zorana Đinđića 81, 18000 Niš, Serbia |
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| Abstract: | Deoxyribonuclease I (DNase I) inhibitory properties of two 1-(pyrrolidin-2-yl)propan-2-one derivatives were examined in vitro. Determined IC50 values of 1-[1-(4-methoxyphenyl)pyrrolidin-2-yl]propan-2-one ( 1 ) (192.13±16.95 μM) and 1-[1-(3,4,5-trimethoxyphenyl)pyrrolidin-2-yl]propan-2-one ( 2 ) (132.62±9.92 μM) exceed IC50 value of crystal violet, used as a positive control, 1.89- and 2.73-times, respectively. Compounds are predicted to be nontoxic and to have favorable pharmacokinetic profiles, with high gastrointestinal absorption and blood-brain barrier permeability. Molecular docking and molecular dynamics simulations suggest that interactions with Glu 39, Glu 78, Arg 111, Pro 137, Asp 251 and His 252 are an important factor for inhibitors affinity toward the DNase I. Determined inhibitory properties along with predicted ADMET profiles and observed interactions would be beneficial for the discovery of new active 1-(pyrrolidin-2-yl)propan-2-one-based inhibitors of DNase I. |
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| Keywords: | DNase I inhibitors enzyme inhibition molecular docking molecular dynamics |
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