Dihydropyrimidones: A ligands urease recognition study and mechanistic insight through in vitro and in silico approach

Farman Ali Khan; Shahbaz Shamim; Nisar Ullah; Muhammad Arif Lodhi; Khalid Mohammed Khan; Kanwal; Farman Ali; Sahib Gul Afridi; Shahnaz Perveen; Ajmal Khan

doi:10.1007/s00044-020-02643-z

Dihydropyrimidones: A ligands urease recognition study and mechanistic insight through in vitro and in silico approach

Farman Ali Khan, Shahbaz Shamim, Nisar Ullah, Muhammad Arif Lodhi^*, Khalid Mohammed Khan, Kanwal, Farman Ali, Sahib Gul Afridi, Shahnaz Perveen, Ajmal Khan^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Scaffold varied dihydropyrimidone derivatives 1–20 were evaluated for their selective urease inhibitory kinetics potential. Compounds 1, 2, 3, 4, 5, 6, and 12 were found to be the most promising urease inhibitors and showed the inhibition (K_i values) within the range of 9.9 ± 0.5 to 18.3 ± 0.4 µM. Lineweaver–Burk plot, Dixon plot and their secondary replots confirm that all these molecules have followed competitive mode of inhibition. Docking arrangements (MOE) revealed that all the ligands bind in the active site and therefore compete with substrate urea. Molecular docking studies of all compounds have confirmed the binding interactions of various ligands with the amino acid residues as well as Ni atoms of active site. Furthermore, these compounds 1–20 were also tested for their cytotoxicity against human neutrophils and plants and were found to be non-toxic.

Original language	English
Pages (from-to)	120-132
Number of pages	13
Journal	Medicinal Chemistry Research
Volume	30
Issue number	1
DOIs	https://doi.org/10.1007/s00044-020-02643-z
State	Published - Jan 2021

Bibliographical note

Publisher Copyright:
© 2020, Springer Science+Business Media, LLC, part of Springer Nature.

Keywords

Dihydropyrimidones
Enzyme kinetics
Michaelis–Menten kinetics
Neutrophil based cytotoxicity
Phytotoxicity

ASJC Scopus subject areas

Pharmacology, Toxicology and Pharmaceutics (all)
Organic Chemistry

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title = "Dihydropyrimidones: A ligands urease recognition study and mechanistic insight through in vitro and in silico approach",

abstract = "Scaffold varied dihydropyrimidone derivatives 1–20 were evaluated for their selective urease inhibitory kinetics potential. Compounds 1, 2, 3, 4, 5, 6, and 12 were found to be the most promising urease inhibitors and showed the inhibition (Ki values) within the range of 9.9 ± 0.5 to 18.3 ± 0.4 µM. Lineweaver–Burk plot, Dixon plot and their secondary replots confirm that all these molecules have followed competitive mode of inhibition. Docking arrangements (MOE) revealed that all the ligands bind in the active site and therefore compete with substrate urea. Molecular docking studies of all compounds have confirmed the binding interactions of various ligands with the amino acid residues as well as Ni atoms of active site. Furthermore, these compounds 1–20 were also tested for their cytotoxicity against human neutrophils and plants and were found to be non-toxic.",

keywords = "Dihydropyrimidones, Enzyme kinetics, Michaelis–Menten kinetics, Neutrophil based cytotoxicity, Phytotoxicity",

author = "Khan, {Farman Ali} and Shahbaz Shamim and Nisar Ullah and Lodhi, {Muhammad Arif} and Khan, {Khalid Mohammed} and Kanwal and Farman Ali and Afridi, {Sahib Gul} and Shahnaz Perveen and Ajmal Khan",

note = "Publisher Copyright: {\textcopyright} 2020, Springer Science+Business Media, LLC, part of Springer Nature.",

year = "2021",

month = jan,

doi = "10.1007/s00044-020-02643-z",

language = "English",

volume = "30",

pages = "120--132",

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T2 - A ligands urease recognition study and mechanistic insight through in vitro and in silico approach

AU - Khan, Farman Ali

AU - Shamim, Shahbaz

AU - Ullah, Nisar

AU - Lodhi, Muhammad Arif

AU - Khan, Khalid Mohammed

AU - Kanwal,

AU - Ali, Farman

AU - Afridi, Sahib Gul

AU - Perveen, Shahnaz

AU - Khan, Ajmal

PY - 2021/1

Y1 - 2021/1

N2 - Scaffold varied dihydropyrimidone derivatives 1–20 were evaluated for their selective urease inhibitory kinetics potential. Compounds 1, 2, 3, 4, 5, 6, and 12 were found to be the most promising urease inhibitors and showed the inhibition (Ki values) within the range of 9.9 ± 0.5 to 18.3 ± 0.4 µM. Lineweaver–Burk plot, Dixon plot and their secondary replots confirm that all these molecules have followed competitive mode of inhibition. Docking arrangements (MOE) revealed that all the ligands bind in the active site and therefore compete with substrate urea. Molecular docking studies of all compounds have confirmed the binding interactions of various ligands with the amino acid residues as well as Ni atoms of active site. Furthermore, these compounds 1–20 were also tested for their cytotoxicity against human neutrophils and plants and were found to be non-toxic.

AB - Scaffold varied dihydropyrimidone derivatives 1–20 were evaluated for their selective urease inhibitory kinetics potential. Compounds 1, 2, 3, 4, 5, 6, and 12 were found to be the most promising urease inhibitors and showed the inhibition (Ki values) within the range of 9.9 ± 0.5 to 18.3 ± 0.4 µM. Lineweaver–Burk plot, Dixon plot and their secondary replots confirm that all these molecules have followed competitive mode of inhibition. Docking arrangements (MOE) revealed that all the ligands bind in the active site and therefore compete with substrate urea. Molecular docking studies of all compounds have confirmed the binding interactions of various ligands with the amino acid residues as well as Ni atoms of active site. Furthermore, these compounds 1–20 were also tested for their cytotoxicity against human neutrophils and plants and were found to be non-toxic.

KW - Dihydropyrimidones

KW - Enzyme kinetics

KW - Michaelis–Menten kinetics

KW - Neutrophil based cytotoxicity

KW - Phytotoxicity

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IS - 1

ER -

Dihydropyrimidones: A ligands urease recognition study and mechanistic insight through in vitro and in silico approach

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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