Acetate platinum(II) compound with 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine that overcomes cisplatin resistance: structural characterization, in vitro cytotoxicity, and kinetic studies

The reaction of silver acetate with cis-[PtI2(dbtp)(2)], where dbtp = 5,7-ditertbutyl-1,2,4-triazolo-[1,5-a] pyrimidine, yielded cis-[Pt(OOCCH3)(2)(dbtp)(2)]center dot dmf (1). The complex has been analyzed by multinuclear magnetic resonance (H-1, C-13, N-15), IR, and Raman. The compound formed two rotamers in CDCl3 and its spatial structures have been optimized using computational calculation. It was found that head-to-tail rotamer (1a) is more stable than its head-to-head counterpart (1b). In vitro antiproliferative activity against four tumor cell lines (A549, T47D, FaDu, and A2780cis) revealed in all cases significant cytotoxicity (IC50 = 0.26-1.80 mu M), possessing IC50 values at least fivefold lower than cisplatin, carboplatin, and oxaliplatin (except A2780cis). The remarkable in vitro activity against T47D and A2780cis suggested the ability to overcome cisplatin resistance in these types of tumor cells. In addition, in vitro toxicity was evaluated against BALB/3T3 and has shown that the lipophilic platinum(II) complex (1) inhibits cell proliferation weaker than cisplatin and oxaliplatin. Additionally, cis-[Pt(OOCCH3)(2)(dbtp)(2)]center dot dmf exhibited selective activity, in contrast to cisplatin or oxaliplatin.