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

<div><p>The reaction of silver acetate with <i>cis-</i>[PtI₂(dbtp)₂], where dbtp = 5,7-ditertbutyl-1,2,4-triazolo-[1,5-<i>a</i>]pyrimidine, yielded <i>cis</i>-[Pt(OOCCH₃)₂(dbtp)₂]·dmf (<b>1</b>). The complex has been analyzed by multinuclear magnetic resonance (¹H, ¹³C, ¹⁵N), 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 (<b>1a</b>) is more stable than its head-to-head counterpart (<b>1b</b>). <i>In vitro</i> antiproliferative activity against four tumor cell lines (A549, T47D, FaDu, and A2780cis) revealed in all cases significant cytotoxicity (IC₅₀ = 0.26–1.80 μM), possessing IC₅₀ values at least fivefold lower than cisplatin, carboplatin, and oxaliplatin (except A2780cis). The remarkable <i>in vitro</i> activity against T47D and A2780cis suggested the ability to overcome cisplatin resistance in these types of tumor cells. In addition, <i>in vitro</i> toxicity was evaluated against BALB/3T3 and has shown that the lipophilic platinum(II) complex (<b>1</b>) inhibits cell proliferation weaker than cisplatin and oxaliplatin. Additionally, <i>cis</i>-[Pt(OOCCH₃)₂(dbtp)₂]·dmf exhibited selective activity, in contrast to cisplatin or oxaliplatin.</p></div