Basic Chalcones: Design, synthesis and evaluation of antiproliferative and other properties

Abstract

A library of basic chalcones were designed and synthesized. The compounds were classified into groups based on the substitution pattern on ring A of the chalcone template. The physicochemical properties of the compounds were assessed and the following biological properties were evaluated: antiproliferative activity against human mammalian cancer cell lines MCF7 and HCT116; antibacterial activity against drug sensitive S. aureus and E. coli; inhibition of the efflux activity of the ATP binding cassette family of transporters p-glycoprotein (Pgp) and breast cancer resistance protein (BCRP). The contribution of the basic group varied according to the type of activity being assessed. Antiproliferative and antibacterial properties were less influenced by the presence of the basic functionality. Monobasic chalcones demonstrated better antiproliferative activities than dibasic chalcones, and there was evidence to indicate that monobasic and dibasic chalcones acted in different ways to bring about antiproliferative activity. The role of the basic functionality was most evident in the inhibition of drug efflux transporters. Basic chalcones were generally better inhibitors of Pgp than BCRP, as compared with non-basic chalcones which were poor Pgp inhibitors.