Flavonoids are polyphenols that are found in numerous edible plant species. Data obtained from preclinical and clini-cal studies suggest that specific flavonoids are chemo-preventive and cytotoxic against various cancers via a multi-tude of mechanisms. However, the clinical use of flavonoids is limited due to challenges associated with their effective use, including (1) the isolation and purification of flavonoids from their natural resources; (2) demonstration of the effects of flavonoids in reducing the risk of certain cancer, in tandem with the cost and time needed for epidemiologi-cal studies, and (3) numerous pharmacokinetic challenges (e.g., bioavailability, drug–drug interactions, and metabolic instability). Currently, numerous approaches are being used to surmount some of these challenges, thereby increas-ing the likelihood of flavonoids being used as chemo-preventive drugs in the clinic. In this review, we summarize the most important challenges and efforts that are being made to surmount these challenges.

In this study we examined the suitability of the-imidazo[4,5-]pyridine ring system in developing novel anticancer and anti-inflammatory agents incorporating a diaryl pharmacophore. Eight 2,3-diaryl-3-imidazo[4,5-]pyridine derivatives retrieved from our in-house database were evaluated for their cytotoxic activity against nine cancer cell lines. The results indicated that the compounds showed moderate cytotoxic activity against MCF-7, MDA-MB-468, K562 and SaOS2 cells, with K562 being the most sensitive among the four cancer cell lines. The eight 2,3-diaryl-3-imidazo[4,5-]pyridine derivatives were also evaluated for their COX-1 and COX-2 inhibitory activity. The results showed that compoundexhibited 2-fold selectivity with ICvalues of 9.2 and 21.8 µmol/L against COX-2 and COX-1, respectively. Molecular docking studies on the most active compoundrevealed a binding mode similar to that of celecoxib in the active site of the COX-2 enzyme.