Journal of Integrative Natural Science (통합자연과학논문집)

The Basic Science Institute Chosun University (조선대학교 기초과학연구원)
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Hologram Quantitative Structure-Activity Relationships Study of N-Phenyl-N'-{4-(4-quinolyloxy)phenyl} Urea Derivatives as VEGFR-2 Tyrosine Kinase Inhibitors

  • Keretsu, Seketoulie (Department of Biomedical Sciences, College of Medicine, Chosun University) ;
  • Balasubramanian, Pavithra K. (Department of Biomedical Sciences, College of Medicine, Chosun University) ;
  • Bhujbal, Swapnil P. (Department of Biomedical Sciences, College of Medicine, Chosun University) ;
  • Cho, Seung Joo (Department of Biomedical Sciences, College of Medicine, Chosun University)
  • Received : 2017.08.22
  • Accepted : 2017.09.25
  • Published : 2017.09.30
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Abstract

Vascular endothelial growth factor (VEGF) is an important signaling protein involved in angiogenesis, which is the formation of new blood vessels from pre-existing vessels. Consequently, blocking of the vascular endothelial growth factor receptor (VEGFR-2) by small molecule inhibitors leads to the inhibition of cancer induced angiogenesis. In this study, we performed a two dimensional quantitative structure activity relationship (2D-QSAR) study of 38 N-Phenyl-N'-{4-(4-quinolyloxy) phenyl} urea derivatives as VEGFR-2 inhibitors based on hologram quantitative structure-activity (HQSAR). The model developed showed reasonable $q^2=0.521$ and $r^2=0.932$ values indicating good predictive ability and reliability. The atomic contribution map analysis of most active compound (compound 7) indicates that hydrogen and oxygen atoms in the side chain of ring A and oxygen atom in side chain of ring C contributes positively to the activity of the compounds. The HQSAR model developed and the atomic contribution map can serve as a guideline in designing new compounds for VEGFR-2 inhibition.

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References

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