Abstract
Natural products represents an important source of new lead compounds in drug discovery research. Several drugs currently used as therapeutic agents have been developed from natural sources; plant sources are specifically important. In the past few decades, pharmaceutical companies demonstrated insignificant attention towards natural product drug discovery, mainly due to its intrinsic complexity. Recently, technological advancements greatly helped to address the challenges and resulted in the revived scientific interest in drug discovery from natural sources. This review provides a comprehensive overview of various approaches used in the selection, authentication, extraction/isolation, biological screening, and analogue development through the application of modern drug-development principles of plant-based natural products. Main focus is given to the bioactivity-guided fractionation approach along with associated challenges and major advancements. A brief outline of historical development in natural product drug discovery and a snapshot of the prominent natural drugs developed in the last few decades are also presented. The researcher’s opinions indicated that an integrated interdisciplinary approach utilizing technological advances is necessary for the successful development of natural products. These involve the application of efficient selection method, well-designed extraction/isolation procedure, advanced structure elucidation techniques, and bioassays with a high-throughput capacity to establish druggability and patentability of phyto-compounds. A number of modern approaches including molecular modeling, virtual screening, natural product library, and database mining are being used for improving natural product drug discovery research. Renewed scientific interest and recent research trends in natural product drug discovery clearly indicated that natural products will play important role in the future development of new therapeutic drugs and it is also anticipated that efficient application of new approaches will further improve the drug discovery campaign.
Highlights
There is a long history of the usage of plant materials for treating human diseases.Several plant species such as opium (Papaver somniferum), myrrh (Commiphora species), and licorice (Glycyrrhiza glabra) have been mentioned on the clay tablets from Mesopotamia in2600 BC; these plants are still used either alone or as one of the ingredients of herbal formulations for the treatment of various diseases
A majority of pharmaceutical companies are showing insignificant interest in natural product research owing to their complex phytochemistry and difficulties in their access and supply [75], a substantial amount of work related to the discovery of therapeutic agents from natural sources are being carried out in academic set-ups and the technical complexities regarding isolation and structural elucidation of bioactive phytoconstituents are being overcome with the cooperation of the chemists globally
Medicinal plants have been used for the treatment of various communicable and non-communicable diseases, and even today represent a rich source of important therapeutic agents as well as new lead compounds
Summary
There is a long history of the usage of plant materials for treating human diseases. Several plant species such as opium (Papaver somniferum), myrrh (Commiphora species), and licorice (Glycyrrhiza glabra) have been mentioned on the clay tablets from Mesopotamia in. In addition to the discovery of new chemical entities (NCEs) for therapeutic application, the natural products provide an important foundation as potential lead compounds for the development of new and more effective drugs through structural modification. The natural compounds obtained from botanical sources may belong to one of the classes including, biologically active compounds directly used as therapeutic agents, lead compounds (with specific biological activity) for development of more potent analogues, compounds whose structures may provide novel pharmacophore that can be converted to druggable compounds or chemical entities to be used as a marker for standardization of crude plant extracts. This article will highlight the modern approaches used for the discovery of natural products from botanical origin by following the proper methods of candidate selection, bioactivity-guided extraction, and fractionation, biological screening, phytochemical characterization to identify potential lead compounds for specific biological activity, and development of analogues of the identified lead through in-silico study and virtual screening techniques (Figure 1)
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