Synthesis and in vitro study of pseudo-peptide thioureas containing α-aminophosphonate moiety as potential antitumor agents

Twenty pseudo-peptide thioureas IIa–l containing α-aminophosphonate moiety were synthesized from the reaction of chiral α-amino carboxamide derivatives Ia–c with O,O′-dialkylisothiocyanato(phenyl)methylphosphonate 5. The synthesized compounds were completely characterized by elemental analysis, physical and spectral (IR, 1H NMR, 13C NMR) data. According to the preliminary studies on antitumor activities, compounds IIa–l could inhibit tumor cells PC3, Bcap37 and BGC823. These compounds displayed low to high activity by MTT assays. Among them, L-IIk, D-IIa and D-IIe were identified as potent inhibitors, with IC50 values ranging from 4.7 to 11.2 μM according to in vitro assay.

Graphical abstractThe pseudo-peptide thioureas containing α-aminophosphonate moiety were synthesized from the reaction of chiral α-amino carboxamide derivatives with O,O′-dialkyl isothiocyanato(phenyl)methylphosphonate. The compounds were screened for their antitumor activities.Figure optionsDownload full-size imageDownload as PowerPoint slide