Applications of the Pharmacophore Concept in Natural Product inspired Drug Design

Abstract

Pharmacophore-based techniques are nowadays an important part of many computer-aided drug design workflows and have been successfully applied for tasks such as virtual screening, lead optimization and de novo design. Natural products, on the other hand, can serve as a valuable source for unconventional molecular scaffolds that stimulate ideas for novel lead compounds in a more diverse chemical space that does not follow the rules of traditional medicinal chemistry. The first part of this review provides a brief introduction to the pharmacophore concept, the methods for pharmacophore model generation, and their applications. The second, concluding part, presents examples for recent, pharmacophore method related research in the field of natural product chemistry. The selected examples show, that pharmacophore-based methods which get mainly applied on synthetic drug-like molecules work equally well in the realm of natural products and thus can serve as a valuable tool for researchers in the field of natural product inspired drug design.

Keywords: computer-aided drug design; natural products; pharmacophore; scaffold hopping; virtual screening.