Differential effects of synthesized 2′-oxygenated chalcone derivatives: modulation of human cell cycle phase distribution Original Research Article

Ten structurally related 2′-oxygenated chalcone derivatives, bearing either hydroxy and/or methoxy substituents on the A and B rings, were synthesized through Claisen–Schmidt condensation. The synthesis procedure was relatively easy and had an acceptable yield. The in vitro cytotoxicities of these compounds against the human tumor cells such as Jurkat, U937 cells, and normal cells PHA stimulated PBMCs were investigated. Among those, compounds 1 (IC50=2.5 μM), 2 (1.7 μM), and 8 (3.2 μM) showed potent inhibitory activity toward Jurkat cell line. In parallel, compounds 1 (6.7 μM), 2 (1.5 μM), and 10 (5.3 μM) showed the highest activity against U937 cell line. However, the chalcones also inhibit the PHA stimulated PBMCs cells, but the IC50 values were relatively high when compared to the tumor cell line values. Studies were also on the effect of synthesized chalcones on the cell cycle phase distribution. In Jurkat cell line, compounds 7 and 9 showed the highest activity and the most striking effect in reduction of the percentage of cells in the S phase, which was associated with an increase of cells in G2/M phase. In U937 cell line, compound 3 increased the proportion of cells in the G0/G1 phase and reduced the proportion in S phase. In contrast, compounds 1, 9, and 10 showed a decrease effect on the percentage of cells in S phase and an increase effect on the percentage of cells in the G2/M phase of the cell cycle. Whereas in the case of PHA stimulated PBMCs, compounds 1, 4, 8, and 10 increased the percentage of cells in G2/M phase, which was associated with a decrease effect in the S phase of the cell cycle.