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http://dx.doi.org/10.5012/bkcs.2007.28.4.561

Adenosine Kinase Inhibitor Design Based on Pharmacophore Modeling  

Lee, Yun-O (Department of Biochemistry, Division of Applied Life Science, Environmental Biotechnology National Core Research Center (EB-NCRC), Gyeongsang National University)
Bharatham, Nagakumar (Department of Biochemistry, Division of Applied Life Science, Environmental Biotechnology National Core Research Center (EB-NCRC), Gyeongsang National University)
Bharatham, Kavitha (Department of Biochemistry, Division of Applied Life Science, Environmental Biotechnology National Core Research Center (EB-NCRC), Gyeongsang National University)
Lee, Keun-Woo (Department of Biochemistry, Division of Applied Life Science, Environmental Biotechnology National Core Research Center (EB-NCRC), Gyeongsang National University)
Publication Information
Bulletin of the Korean Chemical Society / v.28, no.4, 2007 , pp. 561-566 More about this Journal
Abstract
Adenosine kinase (AK) is a ubiquitous intracellular enzyme, which catalyzes the phosphorylation of adenosine (ADO) to adenosine monophosphate (AMP). AK inhibitors have therapeutic potential as analgesic and antiinflammatory agents. A chemical feature based pharmacophore model has been generated from known AK inhibitors (26 training set compounds) by HypoGen module implemented in CATALYST software. The top ranked hypothesis (Hypo1) contained four features of two hydrogen-bond acceptors (HBA) and two hydrophobic aromatics (Z). Hypo1 was validated by 124 test set molecules with a correlation coefficient of 0.905 between experimental and estimated activity. It was also validated by CatScramble method. Thus, the Hypo1 was exploited for searching new lead compounds over 238,819 chemical compounds in NCI database and then the selected compounds were screened based on restriction estimated activity and Lipinski's rules to evaluate their drug-like properties. Finally we could obtain 72 new lead candidates and the two best compound structures from them were posted.
Keywords
Adenosine (ADO); Adenosine kinase (AK) inhibitors; Pharmacophore hypotheses; New lead search; Computer-aided drug design;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
Times Cited By Web Of Science : 7  (Related Records In Web of Science)
Times Cited By SCOPUS : 7
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