In the present study, nine number of different substituted (E)-3-phenyl-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one compounds were synthesized by the condensation reaction of 3,4,5-trimethoxy acetophenone with different substituted benzaldehyde in alcoholic base (sodium hydroxide in ethanol). The yields of the products have been obtained above 80%. The formations of all the (E)-3-phenyl-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-ones have been confirmed by analytical and spectroscopic data. All the assigned spectral values of substituted (E)-3-phenyl-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one compounds are correlated by single and multi-correlation analyses with Hammett sigma constants and F & R parameters. From the regression analyses result, the electronic effects of the substituent were discussed. The evaluation of antimicrobial activity of synthesized chalcones has been screened using Kirby-Bauer method.