통합자연과학논문집 (Journal of Integrative Natural Science)

조선대학교 기초과학연구원 (The Basic Science Institute Chosun University)
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HQSAR Study on Imidazo[1,2-b]pyridazine Derivatives as p38 MAP Kinase Antagonists

  • Bhujbal, Swapnil P. (Department of Biomedical Sciences, College of Medicine, Chosun University) ;
  • Keretsu, Seketoulie (Department of Biomedical Sciences, College of Medicine, Chosun University) ;
  • Cho, Seung Joo (Department of Biomedical Sciences, College of Medicine, Chosun University)
  • 투고 : 2018.05.21
  • 심사 : 2018.06.25
  • 발행 : 2018.06.30
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초록

p38 MAP kinase belongs to the Mitogen-activated protein (MAP) kinase family; a serine/threonine kinase. It plays an important role in intracellular signal transduction pathways. It is associated with the development and progression of various cancer types making it a crucial drug target. Present study involves the HQSAR analysis of recently reported imidazo[1,2-b]pyridazine derivatives as p38 MAP kinase antagonists. The model was generated with Atom (A), bond (B), chirality (Ch), and hydrogen (H) parameters and with different set of atom counts to improve the model. An acceptable HQSAR model ($q^2=0.522$, SDEP=0.479, NOC=5, $r^2=0.703$, SEE=0.378, BHL=97) was developed which exhibits good predictive ability. A contribution map for the most active compound (compound 17) illustrated that hydrogen and nitrogen atoms in the ring A and ring B, as well as nitrogen atom in ring C and the hydrogen atom in the ring D provided positive activity in inhibitory effect while, the least active compound (compound 05) possessed negative contribution to inhibitory effect. Hence, analysis of produced HQSAR model can provide insights in the designing potent and selective p38 MAP kinase antagonists.

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참고문헌

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