Computational design, synthesis and biological evaluation of new heterocyclic compounds as selective tumorogenesis inhibitors

The goal of our project is the design, synthesis and biological evaluation of novel heterocyclic compounds with potential anticancer activity. The research within the project will take two directions: ?) investigation of 2-aminopyridines (and related compounds) as anticancer agents b) derivatization and investigation of privileged structures within natural products, especially isoquinolines and carbolines with anticancer properties. Design and modification of the aminopyridines will be based on structural requirements for ATP-competitive kinase inhibitors. Derivatisation of the privileged structures will initially be governed by “diversity orientated synthesis” principles in order to find a unique structure with anticancer properties. The computational chemistry methods will be applied for the investigation and modelling of targets for anticancer drugs, molecular simulations of target–ligand interactions and the design of new anticancer compounds. Additional investigations will focus on the optimization of physicochemical properties of the compounds. All designed compounds will be synthesised in our laboratories and their activity will be tested on different cancer cell lines: HeLa, Fem-X, K 562. It is expected that this investigations will contribute to better understanding of the pathophysiological cancer related processes on a molecular level, and hopefully will lead to development of new classes of potent, drug-like anticancer compounds.