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Structural Requirements of Minoxidil Analogs for Enhancing Lysyl Hydroxylase Inhibitory Activity
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  • Journal title : KSBB Journal
  • Volume 27, Issue 2,  2012, pp.121-126
  • Publisher : Korean Society for Biotechnology and Bioengineering
  • DOI : 10.7841/ksbbj.2012.27.2.121
 Title & Authors
Structural Requirements of Minoxidil Analogs for Enhancing Lysyl Hydroxylase Inhibitory Activity
Myung, Pyung-Keun; Sung, Nack-Do; Lee, Jae-Heung;
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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 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.
 Keywords
Minoxidil analogs;HQSAR;CoMSIA;Lysyl hydroxylase;Hair growth agent;
 Language
Korean
 Cited by
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