In silico design and synthesis of targeted rutin derivatives as xanthine oxidase inhibitors.
Antioxidant
Molecular docking
Rutin
Xanthine oxidase
Journal
BMC chemistry
ISSN: 2661-801X
Titre abrégé: BMC Chem
Pays: Switzerland
ID NLM: 101741142
Informations de publication
Date de publication:
Dec 2019
Dec 2019
Historique:
received:
21
01
2019
accepted:
02
05
2019
entrez:
7
8
2019
pubmed:
7
8
2019
medline:
7
8
2019
Statut:
epublish
Résumé
Xanthine oxidase is an important enzyme of purine catabolism pathway and has been associated directly in pathogenesis of gout and indirectly in many pathological conditions like cancer, diabetes and metabolic syndrome. In this research rutin, a bioactive flavonoid was explored to determine the capability of itself and its derivatives to inhibit xanthine oxidase. To develop new xanthine oxidase inhibitors from natural constituents along with antioxidant potential. In this report, we designed and synthesized rutin derivatives hybridized with hydrazines to form hydrazides and natural acids to form ester linkage with the help of molecular docking. The synthesized compounds were evaluated for their antioxidant and xanthine oxidase inhibitory potential. The enzyme kinetic studies performed on rutin derivatives showed a potential inhibitory effect on XO ability in competitive manner with IC Taking advantage of molecular docking, this hybridization of two natural constituent could lead to desirable xanthine oxidase inhibitors with improved activity.
Sections du résumé
BACKGROUND
BACKGROUND
Xanthine oxidase is an important enzyme of purine catabolism pathway and has been associated directly in pathogenesis of gout and indirectly in many pathological conditions like cancer, diabetes and metabolic syndrome. In this research rutin, a bioactive flavonoid was explored to determine the capability of itself and its derivatives to inhibit xanthine oxidase.
OBJECTIVE
OBJECTIVE
To develop new xanthine oxidase inhibitors from natural constituents along with antioxidant potential.
METHOD
METHODS
In this report, we designed and synthesized rutin derivatives hybridized with hydrazines to form hydrazides and natural acids to form ester linkage with the help of molecular docking. The synthesized compounds were evaluated for their antioxidant and xanthine oxidase inhibitory potential.
RESULTS
RESULTS
The enzyme kinetic studies performed on rutin derivatives showed a potential inhibitory effect on XO ability in competitive manner with IC
CONCLUSION
CONCLUSIONS
Taking advantage of molecular docking, this hybridization of two natural constituent could lead to desirable xanthine oxidase inhibitors with improved activity.
Identifiants
pubmed: 31384818
doi: 10.1186/s13065-019-0585-8
pii: 585
pmc: PMC6661775
doi:
Types de publication
Journal Article
Langues
eng
Pagination
71Déclaration de conflit d'intérêts
Competing interestsThe authors declare that they have no competing interests.
Références
Diabetes. 2002 Apr;51(4):1118-24
pubmed: 11916934
Ann Intern Med. 1965 Apr;62:639-47
pubmed: 14274828
JAMA. 1965 Jul 5;193:1-6
pubmed: 14297704
J Physiol. 2004 Mar 16;555(Pt 3):589-606
pubmed: 14694147
J Med Chem. 2004 Mar 25;47(7):1739-49
pubmed: 15027865
Nucleosides Nucleotides Nucleic Acids. 2004 Oct;23(8-9):1111-6
pubmed: 15571211
Semin Nephrol. 2005 Jan;25(1):39-42
pubmed: 15660333
Am J Ther. 2005 Jan-Feb;12(1):22-34
pubmed: 15662289
Life Sci. 2005 Mar 4;76(16):1835-47
pubmed: 15698861
Kidney Int. 2005 May;67(5):1739-42
pubmed: 15840020
Cancer Lett. 2005 Sep 28;227(2):133-9
pubmed: 16112416
Cancer Res. 2006 Feb 15;66(4):2257-63
pubmed: 16489029
Pharmacol Rev. 2006 Mar;58(1):87-114
pubmed: 16507884
Clin Pharmacokinet. 2006;45(8):821-41
pubmed: 16884320
Eur J Pharmacol. 2007 Apr 30;561(1-3):63-71
pubmed: 17291486
Recent Pat Inflamm Allergy Drug Discov. 2007 Feb;1(1):69-75
pubmed: 19075968
Bioorg Med Chem Lett. 2009 Nov 1;19(21):5990-3
pubmed: 19800788
J Clin Invest. 1991 Feb;87(2):424-31
pubmed: 1991828
Bioorg Med Chem. 2011 Mar 15;19(6):1950-8
pubmed: 21353569
Pharmacognosy Res. 2010 May;2(3):152-8
pubmed: 21808558
Br J Clin Pharmacol. 2006 Dec;62(6):633-44
pubmed: 21894646
Biochim Biophys Acta. 2014 Sep;1842(9):1502-17
pubmed: 24882753
J Biol Chem. 1989 Jun 15;264(17):9880-4
pubmed: 2542334
Bioorg Med Chem. 2015 Jan 1;23(1):264-71
pubmed: 25496805
Oxid Med Cell Longev. 2015;2015:478039
pubmed: 26137187
Korean J Intern Med. 2015 Jul;30(4):521-30
pubmed: 26161019
Int J Biol Macromol. 2016 Dec;93(Pt A):609-614
pubmed: 27616694
Am J Physiol Renal Physiol. 2017 Mar 1;312(3):F457-F464
pubmed: 28031169
Curr Drug Metab. 2017;18(6):577-593
pubmed: 28302027
Free Radic Biol Med. 2018 May 20;120:160-169
pubmed: 29550332
Drug Chem Toxicol. 2018 May 10;:1-14
pubmed: 29745774
JAMA Intern Med. 2018 Sep 1;178(9):1260-1261
pubmed: 30083702
J Mol Cell Cardiol. 1985 Feb;17(2):145-52
pubmed: 3839024
Inflammation. 1993 Oct;17(5):551-61
pubmed: 8225562
Eur J Pharmacol. 1993 Sep 14;241(2-3):183-8
pubmed: 8243554
Histol Histopathol. 1997 Apr;12(2):513-24
pubmed: 9151140