A simple, and efficient procedure has been developed for the synthesis of novel 2-(4-(hexahydroquinolin-4-yl)phenoxy)-N-arylacetamides and thieno[3′,2′:5,6]pyrimido[1,2-a]quinolines via Michael addition reaction of cyclic enaminones with various 2-(4-(2,2-dicyanovinyl)phenoxy)-N-arylacetamides in the presence of a basic catalyst. The interaction of the compounds with DNA and bovine serum albumin (BSA) was investigated. DNA photocleavage ability was evaluated by agarose gel electrophoresis in UV-A (356 nm). Through inhibitor studies of the most active compounds 5h and 12d, we found that reactive oxygen species play a major role in photocleavage. Molecular docking methods were also used to model the binding of the compound to DNA and BSA, and good agreement was found between experimental and theoretical results. All of these findings suggest that the compounds could be used as a photodynamic therapy agent due to their nucleic acid interactions and photobiological or photochemical properties.