Screening of a library of 4-aryl/heteroaryl-4H-fused pyrans for xanthine oxidase inhibition: Synthesis, biological evaluation and docking studies

Ramandeep Kaur, Fatima Naaz, Sahil Sharma, Samir Mehndiratta, Manish Kumar Gupta, Preet Mohinder Singh Bedi, Kunal Nepali

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

A series of 4-aryl/heteroaryl-4H-fused pyrans was synthesized via multicomponent reaction in a microwave synthesizer. All the pyrans were evaluated for in vitro xanthine oxidase inhibition. Structure-activity relationship was also established. Among the series of 108 compounds, Compound 5n was the most potent displaying remarkable inhibition against the enzyme with an IC50 value of 0.59 μM. Enzyme kinetic study was carried out for the compound 5n to determine the type of inhibition. The study revealed that the compound 5n was a mixed-type inhibitor. Molecular modelling studies were also performed to figure out the interactions of both the enantiomers of 5n with the amino acid residues of the enzyme.

Original languageEnglish
Pages (from-to)3334-3349
Number of pages16
JournalMedicinal Chemistry Research
Volume24
Issue number8
DOIs
Publication statusPublished - Aug 23 2015
Externally publishedYes

Fingerprint

Pyrans
Xanthine Oxidase
Libraries
Screening
Enzyme kinetics
Molecular modeling
Enantiomers
Enzymes
Microwaves
Structure-Activity Relationship
Amino Acids
Inhibitory Concentration 50

Keywords

  • Inhibition
  • Mixed type
  • Molecular modelling studies
  • Pyrans
  • Xanthine oxidase

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry

Cite this

Screening of a library of 4-aryl/heteroaryl-4H-fused pyrans for xanthine oxidase inhibition : Synthesis, biological evaluation and docking studies. / Kaur, Ramandeep; Naaz, Fatima; Sharma, Sahil; Mehndiratta, Samir; Gupta, Manish Kumar; Bedi, Preet Mohinder Singh; Nepali, Kunal.

In: Medicinal Chemistry Research, Vol. 24, No. 8, 23.08.2015, p. 3334-3349.

Research output: Contribution to journalArticle

Kaur, Ramandeep ; Naaz, Fatima ; Sharma, Sahil ; Mehndiratta, Samir ; Gupta, Manish Kumar ; Bedi, Preet Mohinder Singh ; Nepali, Kunal. / Screening of a library of 4-aryl/heteroaryl-4H-fused pyrans for xanthine oxidase inhibition : Synthesis, biological evaluation and docking studies. In: Medicinal Chemistry Research. 2015 ; Vol. 24, No. 8. pp. 3334-3349.
@article{c5fe51b58a3a4fbdb19bb4e1839819d2,
title = "Screening of a library of 4-aryl/heteroaryl-4H-fused pyrans for xanthine oxidase inhibition: Synthesis, biological evaluation and docking studies",
abstract = "A series of 4-aryl/heteroaryl-4H-fused pyrans was synthesized via multicomponent reaction in a microwave synthesizer. All the pyrans were evaluated for in vitro xanthine oxidase inhibition. Structure-activity relationship was also established. Among the series of 108 compounds, Compound 5n was the most potent displaying remarkable inhibition against the enzyme with an IC50 value of 0.59 μM. Enzyme kinetic study was carried out for the compound 5n to determine the type of inhibition. The study revealed that the compound 5n was a mixed-type inhibitor. Molecular modelling studies were also performed to figure out the interactions of both the enantiomers of 5n with the amino acid residues of the enzyme.",
keywords = "Inhibition, Mixed type, Molecular modelling studies, Pyrans, Xanthine oxidase",
author = "Ramandeep Kaur and Fatima Naaz and Sahil Sharma and Samir Mehndiratta and Gupta, {Manish Kumar} and Bedi, {Preet Mohinder Singh} and Kunal Nepali",
year = "2015",
month = "8",
day = "23",
doi = "10.1007/s00044-015-1382-0",
language = "English",
volume = "24",
pages = "3334--3349",
journal = "Medicinal Chemistry Research",
issn = "1054-2523",
publisher = "Birkhause Boston",
number = "8",

}

TY - JOUR

T1 - Screening of a library of 4-aryl/heteroaryl-4H-fused pyrans for xanthine oxidase inhibition

T2 - Synthesis, biological evaluation and docking studies

AU - Kaur, Ramandeep

AU - Naaz, Fatima

AU - Sharma, Sahil

AU - Mehndiratta, Samir

AU - Gupta, Manish Kumar

AU - Bedi, Preet Mohinder Singh

AU - Nepali, Kunal

PY - 2015/8/23

Y1 - 2015/8/23

N2 - A series of 4-aryl/heteroaryl-4H-fused pyrans was synthesized via multicomponent reaction in a microwave synthesizer. All the pyrans were evaluated for in vitro xanthine oxidase inhibition. Structure-activity relationship was also established. Among the series of 108 compounds, Compound 5n was the most potent displaying remarkable inhibition against the enzyme with an IC50 value of 0.59 μM. Enzyme kinetic study was carried out for the compound 5n to determine the type of inhibition. The study revealed that the compound 5n was a mixed-type inhibitor. Molecular modelling studies were also performed to figure out the interactions of both the enantiomers of 5n with the amino acid residues of the enzyme.

AB - A series of 4-aryl/heteroaryl-4H-fused pyrans was synthesized via multicomponent reaction in a microwave synthesizer. All the pyrans were evaluated for in vitro xanthine oxidase inhibition. Structure-activity relationship was also established. Among the series of 108 compounds, Compound 5n was the most potent displaying remarkable inhibition against the enzyme with an IC50 value of 0.59 μM. Enzyme kinetic study was carried out for the compound 5n to determine the type of inhibition. The study revealed that the compound 5n was a mixed-type inhibitor. Molecular modelling studies were also performed to figure out the interactions of both the enantiomers of 5n with the amino acid residues of the enzyme.

KW - Inhibition

KW - Mixed type

KW - Molecular modelling studies

KW - Pyrans

KW - Xanthine oxidase

UR - http://www.scopus.com/inward/record.url?scp=84937525258&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84937525258&partnerID=8YFLogxK

U2 - 10.1007/s00044-015-1382-0

DO - 10.1007/s00044-015-1382-0

M3 - Article

AN - SCOPUS:84937525258

VL - 24

SP - 3334

EP - 3349

JO - Medicinal Chemistry Research

JF - Medicinal Chemistry Research

SN - 1054-2523

IS - 8

ER -