통합자연과학논문집 (Journal of Integrative Natural Science)

조선대학교 기초과학연구원 (The Basic Science Institute Chosun University)
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3D-QSAR Study on Imidazopyridazines Derivatives as Potent Pim-1 Kinase Inhibitors using Region-Focused CoMFA

  • Balasubramanian, Pavithra K. (Department of Biomedical Sciences, College of Medicine, Chosun University) ;
  • Balupuri, Anand (Department of Biomedical Sciences, College of Medicine, Chosun University) ;
  • Cho, Seung Joo (Department of Biomedical Sciences, College of Medicine, Chosun University)
  • 투고 : 2017.04.20
  • 심사 : 2017.06.25
  • 발행 : 2017.06.30
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초록

Proviral Integration site of Moloney (Pim) murine Leukemia virus kinases is a serine/threonine specific protein kinase. It is largely involved in cell survival and proliferation. Pim-1 phosphorylates multiple cellular substrates to inhibit apoptosis and promote cell cycle progression. Over expression of Pim-1 kinase is observed in a range of malignancies and various solid cancers. High level of Pim-1 expression is seen in myeloma, acute myeloid leukemia, prostate cancer and liver carcinomas. Hence, Pim-1 is considered as an interesting cancer target. In the present study, we have performed region-focused CoMFA study on a series of imidazopyridazine derivatives as Pim-1 kinase inhibitors. A statistically acceptable region-focused CoMFA model ($q^2=0.571$; ONC=3; $r^2=0.909$) was developed. The model was then validated using Bootsrapping and progressive sampling. The contour map highlighted the regions favorable to increase the activity. Bulky substitutions in $R^2$ position of the phenyl ring could increase the activity. Similarly, small negative substitution in the $R^1$ position of the Pyridine ring could increase the activity considerably. Our results will be useful to design novel Pim-1 kinase inhibitors of this series.

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참고문헌

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