The present study examines a series of six biologically-active flavonoid and chromanone derivatives by X-ray crystal structure analysis: (E)-3-benzyl­idene-2-phenyl­chroman-4-one, C₂₂H₁₆O₂, I, (E)-3-(4-methyl­benzyl­idene)-2-phenyl­chroman-4-one, C₂₃H₁₈O₂, II, (E)-3-(3-methyl­benzyl­idene)-2-phenyl­chroman-4-one, C₂₃H₁₈O₂, III, (E)-3-(4-meth­oxy­benzyl­idene)-2-phenyl­chroman-4-one, C₂₃H₁₈O₃, IV, (E)-3-benzyl­idenechroman-4-one, C₁₆H₁₂O₂, V, and (E)-3-(4-meth­oxy­benzyl­idene)chroman-4-one, C₁₇H₁₄O₃, VI. The cytotoxic activities of the presented crystal structures have been determined, together with their inter­molecular inter­action preferences and Hirshfeld surface characteristics. An inverse relationship was found between the contribution of C⋯C close contacts to the Hirshfeld surface and cytotoxic activity against the WM-115 cancer line. Dependence was also observed between the logP value and the percentage contribution of C⋯H contacts to the Hirshfeld surface.