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The Korean Society for Biotechnology and Bioengineering (한국생물공학회)
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Structural Requirements of Minoxidil Analogs for Enhancing Lysyl Hydroxylase Inhibitory Activity

Lysyl Hydroxylase의 저해활성을 증가시키기 위한 Minoxidil 유도체들의 구조적인 요건

  • Myung, Pyung-Keun (College of Pharmacy, Chungnam National University) ;
  • Sung, Nack-Do (College of Agriculture and Life Science, Chungnam National University) ;
  • Lee, Jae-Heung (School of Mechanical Engineering, Korea University of Technology and Education)
  • 명평근 (충남대학교 약학대학) ;
  • 성낙도 (충남대학교 농업생명과학대학) ;
  • 이재흥 (한국기술교육대학교 기계정보공학부)
  • Received : 2011.10.21
  • Accepted : 2012.01.17
  • Published : 2012.04.30
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Abstract

In order to explore structural features of minoxidil analogs with a view of enhancing lysyl hydroxylase (LH) inhibitory activity, molecular holographic QSAR (HQSAR) and CoMSIA (comparative molecular similarity indices analysis) were performed. The results from the atomic contributions with optimized the HQSAR 6-2 model indicated that, in case of pyrimidine-1-N-oxide substituent, C2 atom of pyrimidine ring and C'3-C'4 bond of 4-piperidinol group showed the highest impact on the inhibitory activity towards LH enzyme. It was also evident from the information of the optimized CoMSIA F5 model that the inhibitory activity mainly depended on the hydrophobic field contribution (36%) and the hydrogen bond (H-bond) field contribution (49.2%) of substrate molecule. Particularly, it is predicted that the functional groups which disfavor H-bond acceptors in large space around the piperidinol group and also the functional groups which favor the H-bond acceptors at C'4 (& C'5) atom in $R_5$ group play a role for increased inhibitory activity. With this in mind, it is likely that a novel candidate having more improved inhibitory activity on hair growth could be designed in the future.

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References

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