Defeating drug-defying cancers
doi:10.1038/nindia.2011.76 Published online 30 May 2011
Researchers have identified novel organic compounds that could be used to treat drug-resistant cancers. The organic compounds inhibit the activity of a protein that renders the cancer cells resistant to drugs.
Many cancers develop a resistance to chemotherapy drugs. Such resistance is due to the presence of multidrug resistance-associated protein 1 (MRP1), which sits on the membranes of cancer cells. This protein helps cancer cells secrete toxic agents that lead to a decrease in cellular drug concentrations.
To investigate molecules that could inhibit MRP1, the researchers synthesized 48 dihydropyridine derivatives using computer-based models. They then studied the inhibitory effects of each compound through its ability to bind to MRP1, which narrowed the search to ten compounds.
Of the ten compounds chosen, two demonstrated a significant ability to bind and inhibit the activity of MRP1, as well as inhibit human MRP1 expressed in the membrane of insects. One compound was found most potent for its ability to make three hydrogen bonds with MRP1.
The results of the study could be used to design new inhibitors of MRP1. The researchers say that these new dihydropyridine derivatives possess promising characteristics as agents for treating multidrug-resistant cancers.
The authors of this work are from: Medicinal Chemistry Research Division, University College of Pharmaceutical Sciences, and Department of Biotechnology, Kakatiya University, Medicinal Chemistry Research Division, Vaagdevi College of Pharmacy,Warangal, R &D Centre, Divis Laboratories Ltd., Sanath Nagar, Hyderabad, Andhra Pradesh, and Department of Pharmacoinformatics, NIPER, Hajipur, Bihar, India.