Deoxyribonuclease I Inhibitory Properties, Molecular Docking and Molecular Dynamics Simulations of 1-(Pyrrolidin-2-yl)propan-2-one Derivatives
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2021
Authors
Ilić, Budimir S.
Gajić, Mihajlo
Bondžić, Bojan

Džambaski, Zdravko

Kocić, Gordana

Šmelcerović, Andrija
Article (Published version)

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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.
Keywords:
DNase I inhibitors / enzyme inhibition / molecular docking / molecular dynamicsSource:
Chemistry and Biodisversity, 2021, 18, 3, e2000996-Publisher:
- Switzerland :Wiley-Blackwell
Funding / projects:
- Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200026 (University of Belgrade, Institute of Chemistry, Technology and Metallurgy - IChTM) (RS-200026)
- Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200113 (Univeristy of Niš, Faculty of Medicine) (RS-200113)
- The University of Niš (Internal project No. 40)
Note:
- Supporting information: https://cer.ihtm.bg.ac.rs/handle/123456789/4499
- Animation of molecular dynamics simulations - Inhibitor 1/DNase I: https://cer.ihtm.bg.ac.rs/handle/123456789/4500
- Animation of molecular dynamics simulations - Inhibitor 2/DNase I: https://cer.ihtm.bg.ac.rs/handle/123456789/4501
Related info:
- Referenced by
https://cer.ihtm.bg.ac.rs/handle/123456789/4499 - Referenced by
https://cer.ihtm.bg.ac.rs/handle/123456789/4500 - Referenced by
https://cer.ihtm.bg.ac.rs/handle/123456789/4501
DOI: 10.1002/cbdv.202000996
ISSN: 1612-1872; 1612-1880
PubMed: 33529484
WoS: 000618724200001
Scopus: 2-s2.0-85101078713
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IHTMTY - JOUR AU - Ilić, Budimir S. AU - Gajić, Mihajlo AU - Bondžić, Bojan AU - Džambaski, Zdravko AU - Kocić, Gordana AU - Šmelcerović, Andrija PY - 2021 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/4498 AB - 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. PB - Switzerland :Wiley-Blackwell T2 - Chemistry and Biodisversity T1 - Deoxyribonuclease I Inhibitory Properties, Molecular Docking and Molecular Dynamics Simulations of 1-(Pyrrolidin-2-yl)propan-2-one Derivatives VL - 18 IS - 3 SP - e2000996 DO - 10.1002/cbdv.202000996 ER -
@article{ author = "Ilić, Budimir S. and Gajić, Mihajlo and Bondžić, Bojan and Džambaski, Zdravko and Kocić, Gordana and Šmelcerović, Andrija", year = "2021", 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.", publisher = "Switzerland :Wiley-Blackwell", journal = "Chemistry and Biodisversity", title = "Deoxyribonuclease I Inhibitory Properties, Molecular Docking and Molecular Dynamics Simulations of 1-(Pyrrolidin-2-yl)propan-2-one Derivatives", volume = "18", number = "3", pages = "e2000996", doi = "10.1002/cbdv.202000996" }
Ilić, B. S., Gajić, M., Bondžić, B., Džambaski, Z., Kocić, G.,& Šmelcerović, A.. (2021). Deoxyribonuclease I Inhibitory Properties, Molecular Docking and Molecular Dynamics Simulations of 1-(Pyrrolidin-2-yl)propan-2-one Derivatives. in Chemistry and Biodisversity Switzerland :Wiley-Blackwell., 18(3), e2000996. https://doi.org/10.1002/cbdv.202000996
Ilić BS, Gajić M, Bondžić B, Džambaski Z, Kocić G, Šmelcerović A. Deoxyribonuclease I Inhibitory Properties, Molecular Docking and Molecular Dynamics Simulations of 1-(Pyrrolidin-2-yl)propan-2-one Derivatives. in Chemistry and Biodisversity. 2021;18(3):e2000996. doi:10.1002/cbdv.202000996 .
Ilić, Budimir S., Gajić, Mihajlo, Bondžić, Bojan, Džambaski, Zdravko, Kocić, Gordana, Šmelcerović, Andrija, "Deoxyribonuclease I Inhibitory Properties, Molecular Docking and Molecular Dynamics Simulations of 1-(Pyrrolidin-2-yl)propan-2-one Derivatives" in Chemistry and Biodisversity, 18, no. 3 (2021):e2000996, https://doi.org/10.1002/cbdv.202000996 . .