Coumarin-containing aminophosphonates bridged with chiral side chain: synthesis and influence of chirality on cytotoxicity and DNA binding

A series of novel coumarin-containing α-aminophosphonates with two chiral centers were synthesized and a single-crystal structure of compound 8g (8g′, (R)-diethyl ((S)-2-(4-methyl-2-oxo-2H-chromen-7-yloxy)propanamido)(2-bromophenyl)methylphosphonate) was obtained. The in vitro antitumor activities of compound 8a–8g′ against human pulmonary carcinoma cell line (A549), human nasopharyngeal carcinoma (human KB), and human lung adenocarcinoma (MGC-803) cell lines were evaluated. Some compounds showed relatively high cytotoxicity. Compared with 8g, 8g′ exhibited an improved activity against three tumor cells, which was evidenced by the IC50 that was four- to five-fold lower than those for 8g. The influence of chirality was also observed in DNA-binding assay of 8g and 8g′. 8g′ exhibited higher binding constant (1.96 × 103 M−1) as compared to 8g (1.69 × 103 M−1).