α,β-unsaturated ketones are particularly important scaffolds to be utilized in diverse organic reactions including the synthesis of many heterocyclics. Regarding their reactivities as electrophiles, their nature to be utilized as drug candidates are quite limited, although there are natural molecules with diverse pharmacological activities whivh are known to have α,β-unsaturated functionalization. Within this preliminary and random drug-screening based medicinal chemistry study, some (1E,4E)-1,5-diphenylpenta-1,4-dien-3-one derivatives were synthesized and their structures were identified employing chromatographic and spectral methods. The potential of the compounds to inhibit acetylcholinesterase and butyrylcholinesterase enzymes was measured employing modified Ellman’s method. Although the compounds were not found to be potent inhibitors in comparison to current drugs, their activity spectra and selectivity properties displayed their availability to be utilized as important scaffolds for further design of similar α,β-unsaturated systems.