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Keywords:

  • tetrahydropyrido[4,3-d]dihydropyrimidine;
  • thione;
  • synthesis;
  • crystal structure;
  • anticancer activities

Abstract

A new series of tetrahydropyrido[4,3-d]dihydropyrimidine-2-thiones (3a–3x) were designed and synthesized. Their structures were confirmed by 1H NMR, IR, MS and elemental analysis, and the conformation of compound 3j was confirmed by X-ray diffraction. Preliminary bioassays indicated that most of the target compounds presented good antiproliferative activities against leukemic K562 cells, ovarian cancer HO-8910 cells and liver cancer SMMC-7721 cells in vitro. Among them the compounds 3i and 3m afford the best activity, the IC50 of them were 3.22 and 3.65 µg/mL against leukemic K562 cells, respectively, which were lower than the anticancer drug of clinical practice 5-FU (IC50=8.56 µg/mL). Preliminary mechanism of action studies revealed that compound 3i caused DNA fragmentation and activated caspase-3/7 in leukemic K562 cells.