Synthesis and antitumor activities of novel thiourea α-aminophosphonates from dehydroabietic acid

A series of novel thiourea α-aminophosphonate derivatives containing DHA structure was designed and synthesized as antitumor agents. Their inhibitory activities against the NCI-H460 (lung), A549 (lung adenocarcinoma), HepG2 (liver) and SKOV3 (ovarian) human cancer cell lines were estimated using MTT assay in vitro. The screening results revealed that many compounds exhibited moderate to high levels of antitumor activities against the tested cancer cell lines and that most demonstrated more potent inhibitory activities compared with the commercial anticancer drug 5-fluorouracil. The mechanism of compound 5f was preliminarily investigated by acridine orange/ethidium bromide staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining, TUNEL assay, DNA ladder assay and flow cytometry, which indicated that the compound can induce cell apoptosis in A549 cells. [Display omitted] •A series of novel thiourea α-aminophosphonates derivated from dehydroabietic acid were designed and synthesized.•Many compounds showed good antiproliferative activities against tumor cells than the commercial anticancer drug 5-fluorouracil.•Representative compound 5f induced apoptosis.