Synthesis and evaluation of anticancer activity of new 9-acridinyl amino acid derivatives.

A series of eleven 9-acridinyl amino acid derivatives were synthesized using a two-step procedure. Cytotoxicity was tested on the K562 and A549 cancer cell lines and normal diploid cell line MRC5 using the MTT assay. Compounds , , and were the most active, with IC values comparable to or lower than that of chemotherapeutic agent amsacrine. and were especially effective in the A549 cell line (IC ≈ 6 μM), which is of special interest since amsacrine is not sufficiently active in lung cancer patients. Cell cycle analysis revealed that and caused G2/M block, amsacrine caused arrest in the S phase, while and induced apoptotic cell death independently of the cell cycle regulation. In comparison to amsacrine, , , , and showed similar inhibitory potential towards topoisomerase II, whereas only showed DNA intercalation properties. In contrast to amsacrine, , , and showed a lack of toxicity towards unstimulated normal human leucocytes.