Discovery of a Tin-Piperonal-Entecavir Schiff Base Compound That Overcomes Multidrug Resistance by Inhibiting P-Glycoprotein.

The presence of P-glycoprotein in the human intestine represents a significant barrier to effective drug therapy. These proteins form a multidrug-resistant barrier to most drugs, especially those administered orally. Thus, strategies are needed to prepare molecules to combat these resistant proteins and enable an increase in drug efficacy. We developed a novel tin-Schiff base complex using an ultrasonic bath, a new technique in small molecule synthesis. New bond formation was confirmed using ultraviolet and Fourier transform spectroscopies. A computational study was carried out using Absorption, Distribution, Metabolism, Excretion and Toxicity software. The novel tin-entecavir (ETV)-piperonal Schiff base acts as a potent P-glycoprotein inhibitor, which overcomes the multidrug resistance to all drugs that are substrates for P-glycoprotein. Further study showed that the novel tin complex is less toxic than the parent compound at the same dose. The development of this tin-piperonal-ETV Schiff base complex is a major breakthrough for overcoming multidrug resistance barriers and can be applied to other drug molecules.