Effect of N-phenylacetyl L-amino acids on the differentiation of HL-60 cells

A series of N-phenylacetyl-D-amino acid derivatives were prepared and tested against HL-60 cells for differentiation and antiproliferation activities. Among them, five compounds, phenylacetyl-D-valine (17), phenylacetyl-D-leucine (18), phenylacetyl-D-Isoleucine (19), phenylacetyl-D-phenylalanine (21) and phenylacetyl-D-phenylglycine (22) were found to significantly potentiate the all-trans retinoic acid (ATRA)-induced differentiation. The three most effective compounds, 17, 18, and 19 were investigated to ascertain their effects on the cell cycle and were found to behave like ATRA in prohibiting the entry into S phase and G2/M phase. Our findings suggest that when administered together with ATRA, compounds 17, 18, and 19 may have therapeutically beneficial effect in the treatment of acute promyelocytic leukemia (APL).