Title : Design and synthesis of new EF2K inhibitors for the treatment of TNBC and pancreatic cancers and their in vitro release studies from biocompatible natural polymeric particles
Triple-negative breast cancer (TNBC) and pancreatic cancers are aggressive malignancies that respond poorly to treatments and is associated with high rates patient deaths despite surgery and adjuvant chemotherapy. With the currently available chemotherapeutics 5-survival rates of TNBC is 30 % and pancreatic cancer 1-2 % (with median survival only 6 months). Thus, identification of common and clinically significant molecular targets would help developing targeted therapies for these patients. Recently, potent EF2K inhibitors were tested in vitro and in vivo (mice models) of TNBC and panc cancer models using siRNA or microRNA based gene silencing strategy. There is clearly an urgent need to identify better eEF2K inhibitors to target in various cancers. For this purpose, we designed potent new EF2K inhibitors using computational chemistry techniques and synthesized substituted chromenecarboxamide derivatives were confirmed by melting point, FT-IR, 1 H-NMR, 13C-NMR, LC-MS spectral analysis. Furthermore, in vitro release studies of these inhibitors were carried out from biocompatible microgels particles with different size ranges (50 nm -500 μm) that prepared from natural polymers such as hyaluronic acid and/or and polymeric sucrose particles. Identification of EF2K inhibitors may have tremendous impact in the treatment of TNBC, and panc cancer and can be translated into clinic.
•Highlight the importance of protein kinases in the cancer therapy.
•How to design potent new inhibitors and approach to their synthesis and using of drug delivery systems.
•Design new projects with collaboration for cancer therapy.