Research Projects

Drug resistance is the most prominent reason for the failure of anticancer chemotherapy. Tumors are either innately persistent to the drugs used or else are initially drug sensitive but, after remission, recur in drug-resistant form. Frequently, such tumors are obstinate to more than one class of cytostatic drugs. Prominent among possible mechanisms of this multi drug resistance (MDR) are the broad specificity drug efflux pumps of the ABC family. The potential for such proteins to mediate clinical MDR has generated considerable interest in agents able to inhibit their activity and so reverse innate or acquired drug resistance. There are only few highly active inhibitors are known however suffering from severe toxicity. There is of high interest to overcome cancer resistance by developing novel molecules which can provide efficient ABC transporter modulation. To achieve better inhibitors on ABC transporter we have focused on three basic principle of me-dicinal chemistry, 1. Bioisoesteric approach on currently used inhibitor for the synthesis of drug like molecules, 2. Natural product derivatization via a multicomponent reaction (Ugi reaction) approach, 3. Hybrid approach of current inhibitor and natural product. We believe that these basic approaches for drug discovery led us to improve inhibitory activity and the pharmacokinetic profile in comparison to currently used inhibitors.