Synthesis, characterization, and pharmacological evaluation of some metal complexes of quercetin as P-gp inhibitors
Kirankumar Shastrala, Kalam Sirisha, Kumaraswamy Damerakonda, Sharvana Bhava Bandaru Sheshagiri, Hitesh Kumar, Ramu Guda, Mamatha Kasula, Satish Kumar Bedada
Abstract
Abstract Background Six different metal complexes of quercetin (Cu, Zn, Co, Vd, Mo, Ni) were synthesized, purified, and characterized by their physical and spectral (UV, IR) data. They were evaluated for their P-gp (permeability glycoprotein) inhibitory activity by in vitro everted sac method in rats. The apparent permeability of atorvastatin (P-gp substrate) from everted sac of the rat intestine was determined in control, standard (verapamil), and groups treated with quercetin-metal complexes. The drug contents were analyzed by validated RP-HPLC method using a mixture of acetonitrile and water (60:40 v/v) adjusted to pH 2.8 with phosphate buffer as mobile phase. Results In vitro studies revealed that the apparent permeability of atorvastatin (P-gp substrate) across the small intestine is much affected by the treatment with Cu/Co/Ni complexes of quercetin. The mean ± SD and apparent permeability of atorvastatin decreased after pre-treatment with these metal complexes. Conclusions The quercetin Cu/Co/Ni complexes could inhibit P-gp and increase the atorvastatin absorption. Hence, they could be considered P-gp inhibitors.