DESIGN OF NEWER ANALOG OF IMATINIB AS ANTICANCER DRUG TARGETING PROTEIN KINASE RECEPTORAbstract
Protein kinases are key players in cellular signal transduction and perturbations in its activity leads to cancer. Targeting these seems to be sufficient to provoke apoptotic response, thus limiting the process of tumorogenesis. Among kinase inhibitors, imatinib has demonstrated magnificent clinical efficacy. But patients with advanced disease harbor faces resistance. Currently there is requisite of making strategies to overcome resistance and adverse effects in order to provide maximum benefit to the patients. Present work was to develop a new analog of Imatinib with the objective to provide a molecule with best combination of properties, safe and affordable drug. For this purpose Imatinib was taken as a lead molecule which has shown a successful positive bioactivity score of 0.59 for kinase receptor predicted using Molinspiration software. Imatinib was optimized using the concept of Bioisosteric replacement, in order to achieving better affinity towards protein kinase receptor. Newly designed analogs were found in compliance with Lipinski rule of five recommendations for new chemical entity to have good oral bioavailability with no violations. In M (1-6) series of newly designed analogs M4 showed highest score of 0.94, likewise compounds M1, M2, M3, M5 and M6 showed their highest score of 0.86, 0.75, 0.82, 0.86 and 0.76 respectively for protein kinase inhibitor. Target prediction was done using Swiss target prediction software. All the compounds of M (1-6) series show drug targetability for kinase receptor. Compound M4 showed highest bioactivity score as compared to Imatinib can be taken as a lead for future anti cancer studies targeting protein kinase receptor
G. Krishnamoorthy *, S. Shakila Banu, A. M Ismail and R. Senthamarai
Department of Pharmaceutical Chemistry, Periyar College of Pharmaceutical Sciences, Tiruchirappalli, Tamil Nadu, India.
03 November, 2015
21 April, 2016
14 June, 2016
01 July 2016