Structurally modified 'dietary flavonoids': are these viable drug candidates for chemoprevention?

The field of chemoprevention continues to be a heavily researched area since a few decades now. Whereas, the dietary intake of flavonoids occur via daily intakes of fruits, vegetables, herbal preparations, beverages etc, it appears that the active ingredients(s) contained in these dietary sources may not reach the required plasma and/or tissue concentrations in vivo to produce the desired pharmacological response expected of these agents. Akin to the common problems of druggability encountered often times in drug discovery/development scenario, low bioavailability of flavonoids have been attributed to: lack of stability, excessive metabolism, permeability problems, lack of site specificity in distribution, rapid elimination etc. The scope of the review is to assess and put into perspectives salient features of some of the recently reported work on dietary flavonoids including the methylated compounds that showed improved drug-like properties in context with the required features for the lead optimization program rendering a clinical candidate. In addition, it aims to provide some perspectives into the present day considerations for early drug development such as healthy subjects versus cancer patients, single agent versus combination potential with other cancer therapeutics, selection of a cancer indication, potential for drug-drug interaction etc. Although there has been an unabated use of 'dietary flavonoids' with tall order claims for chemoprevention, it may be extremely challenging to confirm it in a clinical setting. Overall, it appears prudent to develop a comprehensive prospective strategy for clinical development and regulatory approval.