Frontiers in Drug Design and Discovery

Volume: 3

Virtual Screening of Compound Libraries Using In silico Three Dimensional Pharmacophores to Aid the Discovery and Design of Anti

Author(s): Apurba K. Bhattacharjee

Pp: 257-292 (36)

DOI: 10.2174/978160805201110703010257

* (Excluding Mailing and Handling)


New chemotherapies to treat malaria and leishmania are needed to combat the growing resistance of available drugs and rapid spread of the diseases in many parts of the world. In the past, drug development efforts have primarily focused on identifying compounds that inhibited the growth of these parasites in culture. With the emergence of structure-based drug design and in silco methodologies, drug development efforts have shifted to targeting specific proteins in the parasites that are unique yet critical for their growth and survival. However, target proteins for potent antimalarial agents are often unknown. The review discusses how in silico methodologies have been successfully applied to virtual screening of compound libraries to aid discovery and design of antimalarial and antileishmanial agents in recent years. The main focus will be on how by developing ligand-based and 3D shape-based pharmacophores from known structure-activity studies, virtual screening of compound libraries are performed to identify potent lead candidates. In silico pharmacophores are geometric distribution of chemical features, such as hydrogen bond acceptor, hydrogen bond donor, aliphatic and aromatic hydrophobic functions, ring aromatic, etc., in three-dimensional space of a molecular structure which are considered responsible for target specific biological activity. Pharmacophores are generated from multiple conformations from a set of molecules having experimental activity data. When the structure of a protein is unknown, this methodology is a very efficient approach to determine the active conformation of a set of molecules.

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