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The multitarget therapeutic strategy, as opposed to the more traditional ‘one disease-one target-one drug’, may hold promise in treating multifactorial neurodegenerative syndromes, such as Alzheimer’s disease (AD) and related dementias. Recently, combining a photopharmacology approach with the multitarget-directed ligand (MTDL) design strategy, we disclosed a novel donepezil-like compound, namely 2-(4-((diethylamino)methyl)benzylidene)-5-methoxy-2,3-dihydro-1<i>H</i>-inden-1-one (<b>1a</b>), which in the <i>E</i> isomeric form (and about tenfold less in the UV-B photo-induced isomer <i>Z</i>) showed the best activity as dual inhibitor of the AD-related targets acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B). Herein, we investigated further photoisomerizable 2-benzylideneindan-1-one analogs <b>1b</b>–<b>h</b> with the unconjugated tertiary amino moiety bearing alkyls of different bulkiness and lipophilicity. For each compound, the thermal stable <i>E</i> geometric isomer, along with the <i>E/Z</i> mixture as produced by UV-B light irradiation in the photostationary state (PSS, 75% <i>Z</i>), was investigated for the inhibition of human ChEs and MAOs. The pure <i>E</i>-isomer of the N-benzyl(ethyl)amino analog <b>1h</b> achieved low nanomolar AChE and high nanomolar MAO-B inhibition potencies (IC₅₀s 39 and 355 nM, respectively), whereas photoisomerization to the <i>Z</i> isomer (75% <i>Z</i> in the PSS mixture) resulted in a decrease (about 30%) of AChE inhibitory potency, and not in the MAO-B one. Molecular docking studies were performed to rationalize the different <i>E</i>/<i>Z</i> selectivity of <b>1h</b> toward the two target enzymes.