IngentaConnect Pharmacophore-Based Screening for the Successful Identification o...

Authors: Langer, Thierry¹; Laggner, Christian²; Rollinger, Judith M.³; Stuppner, Hermann⁴

Source: CHIMIA International Journal for Chemistry, Volume 61, Number 6, June 2007 , pp. 350-354(5)

Abstract:

We report on the impact of pharmacophore-based virtual screening in the field of drug discovery from natural products. Confronted by an increasing number of secondary metabolites and an increasing number of biomolecular targets relevant in the therapy of human disorders, there is clearly the need for efficient data management. Filtering of compounds by virtual screening experiments already showed great effect when dealing with large libraries of potential bioactive molecules. Feature-based 3D pharmacophores have been successfully utilized for database mining in order to retrieve potentially bio-active molecules. However, for the discovery of natural lead candidates, the application of such in silico tools has been so far almost neglected. There seems to be several reasons for this. One concerns the scarce availability of natural product (NP) 3D databases in contrast to synthetic/combinatorial compound libraries; another reason might be the problematic compatibility of NPs with modern robotized high-throughput-screening (HTS) technologies. Additionally, the incalculable availability of pure natural compounds and their often too complex chemistry is claimed to hamper such an approach. Thus, research in this field appears time-consuming, highly complex, expensive, and ineffective. Nevertheless, naturally derived compounds are still among the most favorable sources of new drug candidates. A more rational and economic search for new lead structures originating from nature must therefore be a priority in order to overcome these problems.

Keywords: NATURAL PRODUCTS; PHARMACOPHORES; VIRTUAL SCREENING

Document Type: Research article

DOI: 10.2533/chimia.2007.350

Affiliations: 1: Tel.: +43 512 507 5252, Institute of Pharmacy / Pharmaceutical Chemistry, Leopold-Franzens University of Innsbruck, Innrain, 52c, 6020, Innsbruck, Austria, Inte:LIgand GmbH, Software Engineering and Consulting, Clemens Maria Hofbauergasse, 6, 234 2: Institute of Pharmacy / Pharmaceutical Chemistry, Leopold-Franzens University of Innsbruck, Innrain, 52c, 6020, Innsbruck, Austria 3: Institute of Pharmacy / Pharmacognosy, Leopold-Franzens University of Innsbruck 4: Institute of Pharmacy / Pharmacognosy, Leopold-Franzens University of Innsbruck, Inte:LIgand GmbH, Software Engineering and Consulting, Clemens Maria Hofbauergasse, 6, 2344, Maria Enzersdorf, Austria

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Pharmacophore-Based Screening for the Successful Identification of Bio-Active Natural Products