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DOI: 10.1055/s-0030-1264217
In silico strategy for the identification of cyclooxygenase inhibitors from the Thai medicinal mixture Prasaplai
Prasaplai is a medicinal plant mixture that is used in Thailand to treat primary dysmenorrhea [1] which is characterized by painful uterine contractility and caused by a significant increase of prostaglandin release [2,3]. Cyclooxygenase (COX) represents a key enzyme in the formation of prostaglandins. Former studies revealed that extracts of Prasaplai inhibit COX-1 and COX-2 [4]. The major aim of this study was to predict which compounds of the complex mixture of natural products might be responsible for the COX inhibitory activity. Therefore, a comprehensive literature survey for known constituents of Prasaplai was performed. A multiconformational 3D database was generated comprising 683 molecules. Virtual parallel screening using a set of six validated pharmacophore models for COX inhibitors [5] was performed resulting in a hit list of 166 compounds. 46 Prasaplai components with already determined COX activity were used for the external validation of this set of COX pharmacophore models. 57% of these components were predicted correctly by the pharmacophore models, i.e. virtual hits with inhibitory activity on COX as well as inactive non-hits. The findings of this theoretical study confirm that the virtual approach provides a helpful tool for the fast identification of novel COX inhibitors [6].
Acknowledgements: This work was granted by the Austrian Science Foundation (B89-B03).
References: 1. National Drug Committee (2006) List of Herbal Medicinal Products A.D. 2006; Chuoomnoom Sahakorn Karnkaset Publisher. Bangkok.
2. Connolly, T.P. (2004) Clin. Med. Res. 1:105–110.
3. Hayes E.C., Rock J.A. (2002) Obstet. Gynecol. Surv. 57:768–780.
4. Nualkaew, S., Tiangda, C., Gritsanapan, W., Bauer, R., Nahrstedt, A. (2005) 53rd Annual Congress of the Society for Medicinal Plant Research, Florence, p 359.
5. Schuster, D. et al. (2010) Mol. Inf. 29:75–86. 6. Waltenberger, B. et al. (2010) submitted.