Pure and Applied Chemistry

Abstract: Natural products have been a rich source of lead identification for drug discovery and development. Over the last two decades, the impetus for natural product-based lead discovery in pharmaceutical industry has declined, resulting in a productivity and innovation crisis. Most of the focus is now on high-throughput screening of synthetic libraries of compounds against defined biological targets; however, discovery of new molecular entities (NMEs) is still declining in this postgenomic era. With the availability of modern purification, characterization, and yield optimization techniques, and with an established intellectual property rights (IPR) regime, it is now possible to circumvent the problems once associated with natural product-based drug discovery. Our work demonstrates that natural products can lead to cost-effective identification of lead molecules against a defined molecular target. During our recent studies, novel classes of urease and α-glucosidase inhibitors were initially obtained from medicinal plants, and based on these novel structural leads, synthetic libraries of structural analogues were synthesized for structure–activity relationship (SAR) studies. These synthetic analogues have shown potent inhibitory activities against the target enzymes, and their mechanisms of action were studied by kinetic, computational, and NMR-based methods.