ABSTRACT
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.
ABSTRACT
In the present work cross-linked guar gum microspheres were prepared for colon specific delivery of ornidazole. Development and optimization of guar gum microspheres for colonic drug delivery was carried out using a 2(4) factorial design based on four independent variables. Microspheres were prepared by emulsification method using glutaraldehyde as cross-linking agent. Morphology and surface characteristics of the formulations were determined by scanning electron microscopy. Particle size of the guar gum microspheres was determined by particle size analyzer. In vitro drug-release studies were performed in conditions simulating stomach-to-colon transit in the presence and absence of rat cecal contents. Only a small fraction of drug was released at acidic pH; however, the release of drug was found to be higher in the presence of rat cecal contents, indicating the susceptibility of guar gum matrix to colonic enzymes released from rat cecal contents. The significance of differences was evaluated by analysis of variance (ANOVA). Differences were considered statistically significant at p<0.05.
