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

Abstract

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]·dmf (1). 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 (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 μM), 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]·dmf exhibited selective activity, in contrast to cisplatin or oxaliplatin.

Graphical abstract

Keywords:

• Platinum(II) complexes
• Acetate
• ¹⁵N NMR
• Hydrolysis
• In vitro cytotoxicity
• Computational calculation

Acknowledgements

The authors wish to thank the Wroclaw Centre for Networking and Supercomputing, and the Academic Computer Centre Cyfronet AGH Cracow for generous allotment of computational facilities.

Disclosure statement

No potential conflict of interest was reported by the authors.

Notes

Dedicated to Professor Rudi van Eldik with the very best wishes of the authors for all his future endeavors.