Chapter 5 - Application of Computation in Building Dereplicated Phytochemical Libraries

Abstract

This chapter looks into the applications and impacts of computational methods in dereplication of phytochemicals, especially in relation to formation of dereplicated phytochemical libraries for high-throughput screening (HTS). Phytochemical libraries are classified into two major categories: one is a collection of real compounds isolated and identified from plant sources for HTS utilizing automated in vitro assays, and the other is a compilation of two- and three-dimensional structures of phytochemicals for virtual (also known as in silico) screening. To build a compound library comprising phytochemicals, it is important to ensure that the library only contains dereplicated compounds, and thus, enriches the chemical diversity and increases the chances for success in any drug-discovery programme. In recent years, with the advent and advancement of modern separation and identification techniques and tools, where operations are significantly enhanced by various computational tools, the ease and quality of dereplication processes have increased remarkably. This has led to generation of several high quality phytochemical libraries. The production of phytochemical libraries is often a more cumbersome and lengthier process than that of synthetic combinatorial libraries, but they offer better chemical diversity, and therefore, are still popular in the drug-discovery scene.