Solution Phase Combinatorial Synthesis and Screening of Mini Libraries of Arylchalcones for Antibacterial Activity

Abstract
The solution-phase combinatorial synthesis of aryl chalcones was studied by synthesizing a 6x4 array mini library. The mini libraries of chalcones were synthesized by condensation of 4-substituted acetophenones and various aryl/heteroaryl carbaldehydes. All the synthesized mini libraries were screened for antibacterial activity using serial dilution method. The mini-libraries 3{1a,2a–d}, 3{1b,2a–d}, 3{1a–f,2a} and 3{1a–f,2c} were found to be most active of the synthesized mini libraries. The common elements present in the identified pool of interest were used to individually synthesize four compounds which were individually subjected to antibacterial activity evaluation. The compound 3-(4-chlorophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one exhibited significant activity that was better than that of the other three compounds synthesized. The anti-bacterial activity of the identified hit was also found to be better than all mini-libraries, indicating utility of combinatorial synthesis and the assumption there in for lead identification.

Keywords
Combinatorial • Chalcones • Antibacterial • Leads