Limitation of Algar–Flynn–Oyamada reaction using methoxy substituted chalcones as reactants and evaluation of the newly transformed aurones for their biological activities

The study describes newly synthesized 7-(1-Benzyl-1,2,3,6-tetrahydro-pyridin-4-yl)-4,6-dimethoxy aurones (SJA 1–14) obtained as final compounds by the oxidative cyclisation of chalcone intermediates in the presence of alkaline hydrogen peroxide catalyst. Their structures were confirmed by spectral analysis and were further evaluated for their in vitro antioxidant and anticancer activities. To support their physicochemical characteristics, distribution coefficients (log D_7.4) and oxidation potentials (Epa) were determined. Among the test compounds, SJA 8 and SJA 11 were found cytotoxic to MCF-7, T47D and MDA MB-231 in the IC₅₀ range of 16.63 ± 1.00–43.93 ± 2.09 µM when compared to doxorubicin in the IC₅₀ range of 0.23 ± 0.03–8.32 ± 0.46 µM. Further studies performed with SJA 8 and SJA 11 on MCF-7 showed that they significantly increased the apoptotic index as compared to the control and displayed a G₀/G₁ phase arrest of the cell cycle. It was observed that synthesised aurones possessing para substitution on ring B showed cytotoxic activity and possessed log D_7.4 in the range of 2.5–3.2. Conversely, radical scavenging activity of aurones was in the IC₅₀ range of 71.67 ± 0.24 to >1000 µM when compared to ascorbic acid and quercetin in the IC₅₀ range of 15.46 ± 1.30–34.42 ± 0.03 µM. However, their low antioxidant potential was supported by their high Epa values in the range of 0.926–1.008 V when compared to standard antioxidants. Further studies on N-benzyl tetrahydropyridinyl-4,6-dimethoxy substituted aurones would create a platform for understanding their optimum structural features and the extent to which they may be useful as anticancer agents.