Cellular targets of natural products

Abstract

Natural products have evolved, at least in part, to bind to biological macromolecules, particularly proteins. As a result, natural products are able to interact with many specific targets within the cell. Indeed for many years this has been central in the drug development process. Today, however, natural products are finding increasing use as probes to interrogate biological systems as part of chemical genomics and related research. In order to demonstrate the utility of natural products in these efforts, the biological activities of many of the major classes of natural products is discussed, according to the cellular organelle and localisation of their specific molecular targets. Emphasis is given to newly discovered compounds and activities that either provide interesting insights into a specific biological function, or that form the basis for potentially new therapeutic approaches.

In vitro cytotoxicity screening of wild plant extracts from Saudi Arabia on human breast adenocarcinoma cells

“…There has long been standing interest in the identification of natural products for the treatment of various diseases for thousands of years. Natural products possess immense pharmacological significance in the development of drugs (Dixon et al, 2007;Baker et al, 2007;Harvey, 2008) including cancer (Graham et al, 2000;Figueroa-Hernández et al, 2005;Madhuri and Pandey, 2009;Tan et al, 2011;Newman and Cragg, 2012;Kuno et al, 2012), and were discovered through plant bioprospecting (Mann, 2002). The majority of drug candidates, such as paclitaxel, etoposide, camptothecin, vinca alkaloids, indole alkaloids, podophyllotoxin derivatives, etoposide and teniposide, currently used in clinical cancer chemotherapy, were originally derived from plants.…”

Fusarielin A as an Anti-angiogenic and Anti-proliferative Agent: Basic Biological Characterization

“…Generally, isolation of bioactive natural products based on some specific biological activity requires a specific bioassay system that reflects the corresponding biological activity. [1][2][3][4][5][6] For example, tubulin function disruptors (inhibitors of tubulin polymerization or depolymerization) have generally been isolated with the aid of microtubule assembly assay, [1][2][3][4] while signal transduction inhibitors have generally been isolated with the guidance of inhibition assays of specific enzymes, such as protein kinases and phosphatases. 5,6) On the other hand, a bioassay system that could simultaneously detect various kinds of cell function modulators, including cell proliferation inhibitors, cell differentiation modulators, signal transduction modulators, and so on, would be a superior tool to discover unique bioactive compounds, even if it provided no information as to their specific molecular targets/mechanisms.…”

Antiviral drug discovery: broad-spectrum drugs from nature

“…To base the search for treatments of a given medical condition on natural products has a variety of advantages: Natural products exhibit a large structural diversity and complexity that remains unmatched by other drug formats 138,139 . Diversity of chemical matter is an important prerequisite to address the diversity of biological target space, in particular in the context of phenotypic screenings that capture full biological pathways rather than single protein domains [140][141][142] . The structural complexity of natural products, often regarded as a drawback with respect to synthetic accessibility, has been successfully mastered due to vastly improved methods of organic synthesis and/or genetic engineering 143 .…”