Design, synthesis and antitumor activity evaluation of pyrimidine derivatives containing 4-hydroxypiperidine group

In the current study, a series of pyrimidine derivatives containing the 4-hydroxypiperidine group were designed and synthesized, and the antiproliferative activity of these compounds against four human tumor cell lines (MGC-803, PC-3, A549, H1975) was evaluated by MTT method in vitro. Most of the compounds have moderate anti-proliferative activities, among which compound 17i displayed the most excellent anti-proliferative activity, with IC50 value of 3.89 +/- 0.57 mu M against H1975 cell. Preliminary antitumor mechanism studies revealed that compound 17i could inhibit colony formation and cell migration of H1975 cells. Furthermore, compound 17i induced H1975 cells apoptosis in a dose-dependent manner and H1975 cell cycle arrest in S phase to inhibit cell proliferation. These results indicates that compound 17i could be a promising lead for further studies. [GRAPHICS] .