Kranthi Raj K.1, Pathak L.P.2, Muttineni Ravikumar3, Ramachandrana D.4
1Acharya Nagarjuna University, P.G center, Nuzvid, 521201, Andhra Pradesh, India
2National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 5000 37, Andhra Pradesh, India
3Bioinformatics Division, Environmental Microbiology Lab, Department of Botany, Osmania University, Hyderabad 500007, Andhra Pradesh, India
4
Received : - Accepted : - Published : 21-12-2010
Volume : 2 Issue : 2 Pages : 20 - 50
Int J Drug Discov 2.2 (2010):20-50
DOI : http://dx.doi.org/10.9735/0975-4423.2.2.20-50
Keywords : Leukotriene A4 hydrolase (LTA4H), Pharmacophore
Conflict of Interest : None declared
Leukotriene A4 hydrolase (LTA4H) is a hydrolase with a bifunctional zinc enzyme, which plays a role in inflammation. LTA4H may also play an important role in carcinogenesis, especially chronic inflammation-associated carcinogenesis. In this study, chemical feature based pharmacophore models based on 22 currently available LTA4H inhibitors have been developed with the aid of HipHop and HypoRefine modules within Catalyst program package. 3D pharmacophore model developed was, characterized by distinct chemical features such as Hydrogen-bond acceptor (HA), Hydrogen-bond donor (HD), Hydrophobic aliphatic (HPAli), Hydrophobic aromatic (HPAr) that are found to be responsible for the activity of the LTA4H inhibitors. The correlation coefficient, root mean square deviation and cost difference were 0.92, 1.0867 and 53.62 respectively, suggesting that a highly predictive pharmacophore model was successfully obtained. The results of our study provide a valuable tool in designing new leads with desired biological activity for virtual screening.
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