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.
Highlights
Evaluation of deoxyribonuclease I inhibitionCompounds were assessed for inhibitory properties against DNase I from bovine pancreas
DNase I from bovine pancreas, DNA, DMSO and perchloric acid were purchased from Sigma-Aldrich
Evaluation of in vitro enzyme inhibition was conducted as spectrophotometric measurement of acid-soluble nucleotides formation at 260 nm, according to our previously published procedures[9 - 13] Studied compounds were assayed for DNase I inhibitory activity at concentration of 200 μM. Those exhibiting inhibition greater than 50% at these concentrations were tested in a broader series of concentrations to allow calculation of IC50 values
Summary
Compounds were assessed for inhibitory properties against DNase I from bovine pancreas. Evaluation of in vitro enzyme inhibition was conducted as spectrophotometric measurement of acid-soluble nucleotides formation at 260 nm, according to our previously published procedures[9 - 13] Studied compounds were assayed for DNase I inhibitory activity at concentration of 200 μM. Those exhibiting inhibition greater than 50% at these concentrations were tested in a broader series of concentrations to allow calculation of IC50 values. IC50 curves were generated using three concentrations of studied compounds (200, 150 and 100 μM).
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
