DYRK1A kinase inhibitors with emphasis on cancer.

Various types of cancers (including gliomas, melanomas, and esophageal, pancreas and non-small-cell lung cancers) display intrinsic resistance to pro-apoptotic stimuli, such as conventional chemotherapy and radiotherapy, and/or the activation of a multidrug resistance phenotype, which are major barriers to effective treatment and lead to poor patient prognosis. The DYRK1A kinase is directly implicated in the resistance of cancer cells to pro-apoptotic stimuli and drives several pathways that enhance proliferation, migration, and the reduction of cell death, leading to very aggressive biological behavior in cancer cell populations. The DYRK1A kinase is also implicated in neurological diseases and in neoangiogenic processes. Thus, the DYRK1A kinase is of great interest for both cancer and neuroscience research. During the last decade, numerous compounds that inhibit DYRK1A have been synthesized. The present review discusses the available molecules known to interfere with DYRK1A activity and the implications of DYRK1A in cancer and other diseases and serves as a rational analysis for researchers who aim to improve the anti-DYRK1A activity of currently available compounds.

Lycorine and its derivatives for anticancer drug design.

Amaryllidaceae alkaloids are extensively studied for their biological activities in several pharmaceutical areas, including, for example, Alzheimer's disease for which galanthamine has already reached the market. Among this chemical family, lycorine displays very promising anti-tumor properties. This review first focuses on the chemical diversity of natural and synthetic analogues of lycorine and their metabolites, and then on mechanisms of action and biological targets through which lycorine and its derivatives display their anti-tumor activity. Our analysis of the structure-activity relationships of this family of compounds highlights the existence of various potential leads for the development of novel anticancer agents.

Natural polyphenols that display anticancer properties through inhibition of kinase activity.

Over eleven hundred publications reporting anticancer activities of polyphenols have appeared in the peer-reviewed literature. In addition, a search of the PubMed database using "polyphenols - cancer - review" as keywords produced over 320 hits for review articles (July 2009). Polyphenol anticancer activities include, among others, anti-oxidative, pro-apoptotic, DNA damaging, anti-angiogenic, and immunostimulatory effects. Targeting specific protein kinases to combat cancer represents a major focus of oncology research within the so-called targeted therapy approach. An exhaustive search of the PubMed database (July 2009) using "polyphenols - cancer - kinases" as keywords resulted in more than 130 hits, half of them having been published within the past five years. Furthermore, the PubMed database contains 25 reviews on the subject of anti-kinase activity of some specific polyphenols, including mainly curcumin and the green tea polyphenol (-)-epigallocatechin 3-gallate (EGCG). However, no attempt has been made yet to review this area of research in a comprehensive, general manner. The current review therefore aims to highlight those anticancer polyphenols that target specific kinases in various types of cancer. The present review also provides an in-depth analysis of polyphenol structure- activity relationships in relation to their anticancer activities and specific kinase targeting. Lastly, a number of polyphenols are identified as potential antitumor agents that could be used to combat biologically aggressive cancers, including metastasizing cancers, through the targeting of specific kinases.