Combinatorial synthesis, lead identification, and antitumor study of a chalcone-based positional-scanning library

Abstract

A 175-member chalcone library was designed and synthesized from seven differently substituted acetophenones (A1-A7) and 25 differently substituted aryl or heteroaryl aldehydes (B1-B25). Potential lead compounds were identified by deconvolution of a two-dimensional library matrix via positional scanning, and the members of the most-active sub-libraries were synthesized and screened against crown-gall tumors with the aid of the potato-disc assay. The resulting hits gave rise to significant antitumor activities, with no antibacterial effect on the tumor-producing bacterium Agrobacterium tumefaciens. Two identified lead structures, (2E)-3-(2-chlorophenyl)-1-phenylprop-2-en-1-one (A1B9) and the hydroxy analogue (2E)-3-(2-chlorophenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one (A2B9), are promising candidates to be developed into highly effective anticancer chemotherapeutics. © 2007 Verlag Helvetica Chimica Acta AG, Zürich.