Synthesis and Biological Evaluation of Novel 2- benzoylbenzofurans as Potential Anticancer Agents

Abstract

The heterocyclic benzofuran moiety is a privileged chemical entity that has been utilized in the development of novel pharmaceuticals. Benzofurans have been studied for therapeutic uses in cancer, cardiovascular diseases, antimicrobial, psychotic disorders, renal disorders and inflammation. Another privileged structure in drug development is the piperazine unit. The addition of this structure has been shown to greatly improve water solubility making this template well utilized in many clinically successful drugs. Our group’s interest in the development of anticancer agents has pushed us to discover the therapeutic potential of piperazine bearing benzofurans. A recent report involving the synthesis and evaluation of an piperazino N,N-diethyl benzofuran has peaked our interest due to the simplicity of synthesis and good cytotoxicity properties. In this regard, we sought to synthesis and evaluate a series of piperazine substituted 2-benzoylbenzofurans. Through a two-step Rap-Stoermer condensation between salicylaldehydes and phenacyl bromide prior to ipso substitution with piperazine, numerous candidate compounds have been synthesized. These compounds have been evaluated via MTT cell proliferation assay for their cytotoxic properties on six cancer cell lines: 4T1, 67NR, MIA PaCa-2, MCF7, MDAMB-231, and WiDr. Compounds 2.36 and 2.40 were found to be the most potent with IC50 values ranging from ~2-4 M and ~2-8 M across all cell lines. The synthesis and in vitro evaluation studies are presented in this thesis.