Design, synthesis and biological evaluation of naphthalenebenzimidizole platinum (II) complexes as potential antitumor agents

A serial of naphthalenebenzimidizole-Pt complexes 1-6 were designed and synthesized as antitumor agents. In vitro antitumor assay results showed that complexes 1-6 exhibited moderate to high anti-proliferative activity against Hela, HepG2, SKOV-3, NCl-H460, BEL-7404 and A549 cancer cell lines, while they displayed obvious sensitivity and selectivity against SMMC-7721 and U251 cell lines and low toxicity against normal HL-7702 cells, in comparison with cisplatin. In vivo antitumor assay results indicated that complex 1 and 5 exhibited important in vivo antiproliferative activity in the NCI-460 and SMMC-7721 models, in comparison with cisplatin, respectively. Complexes 1 and 5 exhibited better antiproliferative activity against A549CDDP and SKOV3CDDP cell lines than cisplatin, with IC50 values of 6.98 +/- 0.47 mu M, 5.62 +/- 0.88 mu M and 13.13 +/- 2.11 mu M, 5.30 +/- 0.33 mu M, respectively, while they displayed potential antiproliferation against A549 and SKOV3 cell lines, with IC50 values of 7.32 +/- 0.51 mu M, 5.19 +/- 0.49 mu M and 14.92 +/- 0.11 mu M, 12.19 +/- 0.92 mu M, indicating the introduction of naphthalenebenzimidizole into platinum-metal system may overcome the resistance. Mechanistic studies showed that the representative complexes 1 and 5 exerted the antitumor effect mainly by the obvious covalent binding with DNA and the upregulation of the expression level of intracellular topo I, showing different action mechanism from cisplatin. (C) 2020 Elsevier Masson SAS. All rights reserved.