TY - JOUR
T1 - Structural insights into the polypharmacological activity of quercetin on serine/threonine kinases
AU - Baby, Bincy
AU - Antony, Priya
AU - Al Halabi, Walaa
AU - Al Homedi, Zahrah
AU - Vijayan, Ranjit
N1 - Publisher Copyright:
© 2016 Baby et al.
PY - 2016/9/27
Y1 - 2016/9/27
N2 - Polypharmacology, the discovery or design of drug molecules that can simultaneously interact with multiple targets, is gaining interest in contemporary drug discovery. Serine/threonine kinases are attractive targets for therapeutic intervention in oncology due to their role in cellular phosphorylation and altered expression in cancer. Quercetin, a naturally occurring flavonoid, inhibits multiple cancer cell lines and is used as an anticancer drug in Phase I clinical trial. Quercetin glycosides have also received some attention due to their high bioavailability and activity against various diseases including cancer. However, these have been studied to a lesser extent. In this study, the structural basis of the multitarget inhibitory activity of quercetin and isoquercitrin, a glycoside derivative, on serine/threonine kinases using molecular modeling was explored. Structural analysis showed that both quercetin and isoquercitrin exhibited good binding energies and interacted with aspartate in the highly conserved Asp-Phe-Gly motif. The results indicate that isoquercitrin could be a more potent inhibitor of several members of the serine/threonine kinase family. In summary, the current structural evaluation highlights the multitarget inhibitory property of quercetin and its potential to be a chemical platform for oncological polypharmacology.
AB - Polypharmacology, the discovery or design of drug molecules that can simultaneously interact with multiple targets, is gaining interest in contemporary drug discovery. Serine/threonine kinases are attractive targets for therapeutic intervention in oncology due to their role in cellular phosphorylation and altered expression in cancer. Quercetin, a naturally occurring flavonoid, inhibits multiple cancer cell lines and is used as an anticancer drug in Phase I clinical trial. Quercetin glycosides have also received some attention due to their high bioavailability and activity against various diseases including cancer. However, these have been studied to a lesser extent. In this study, the structural basis of the multitarget inhibitory activity of quercetin and isoquercitrin, a glycoside derivative, on serine/threonine kinases using molecular modeling was explored. Structural analysis showed that both quercetin and isoquercitrin exhibited good binding energies and interacted with aspartate in the highly conserved Asp-Phe-Gly motif. The results indicate that isoquercitrin could be a more potent inhibitor of several members of the serine/threonine kinase family. In summary, the current structural evaluation highlights the multitarget inhibitory property of quercetin and its potential to be a chemical platform for oncological polypharmacology.
KW - Docking
KW - Isoquercitrin
KW - Polypharmacology
KW - Quercetin
KW - Serine/threonine kinases
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U2 - 10.2147/DDDT.S118423
DO - 10.2147/DDDT.S118423
M3 - Article
C2 - 27729770
AN - SCOPUS:84989170530
SN - 1177-8881
VL - 10
SP - 3109
EP - 3123
JO - Drug Design, Development and Therapy
JF - Drug Design, Development and Therapy
ER -