Remarkable structural diversity and drug-likeness of molecular scaffolds, identified in natural compounds, provides a basis for the design of novel natural product-derived compound libraries for drug discovery [1-2].
Life Chemicals presents its Natural Product-like Compound Library, containing 2 subsets generated through the following approaches:
- Similarity based search against commercial databases of Timetek, Specnet, Analyticon, Selleck: 900 compounds in stock.
- Superposition of chemoinformatics and substructure search methods, applied to the entire Life Chemicals Compound Collection with the overlapping items selection [1, 3]: 2,000 compounds in stock.
Natural Products-like Compounds Library by Similarity Search
The Library was designed by means of 2D fingerprint similarity filtering of the Life Chemicals HTS Compound Collection using commercial databases of Timetek, Specnet, Analyticon, Selleck as the reference sets. A Tanimoto 85% similarity cut-off was applied to obtain about 900 stock available compounds.
Natural Products-like Compounds Library by Chemoinformatics and Substructure Search
Overlapping both collections obtained after analysis of the Life Chemicals Stock Collection by two different methods - chemical descriptors calculation (7,300 compounds) and natural-likeness scoring (9,700 compounds), a chemical space of about 2,000 compounds with good characteristics in both studies was obtained:
Descriptor-based selection method
The selection has been done in two steps:
- Substructure search for natural-like scaffolds in the Life Chemicals Stock Collection. About 62,000 were selected from about 380,000 compounds.
- Validation of the method and calculation of the parameters listed in Table1 for Drugs (COBRA), Pure Natural Products (PNP, MNP), NPs and Derivatives/Analogs (SNP), and NP-Based Combinatorial Compounds (NatDiv).
Table 1. Mean values of descriptors which play the most important role in characterization of natural products.
Natural product-likeness calculator
Fig. 1. Standard cross-platform view of Taverna 2.0 software with a schema of connections between template files, natural-product likeness calculator and query file the HTS Compound Library
Fig. 2. Natural product-likeness scorer. Distribution of real natural products.
- Properties and Architecture of Drugs and Natural Products Revisited. Kristina Grabowski and Gisbert Schneider.
- Matthew E Welsch, Scott A Snyder and Brent R Stockwell, Current Opinion in Chemical Biology 2010,141–15
- Natural Product-likeness Score and Its Application for Prioritization of Compound Libraries. Peter Ertl, Silvio Roggo, and Ansgar Schuffenhauer. J. Chem. Inf. Model. 2008, 48, 68-74
- Scaffold diversity of natural products: inspiration for combinatorial library design. Kristina Grabowski,a Karl-Heinz Baringhausb and Gisbert Schneider