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  3. Bridging pyrimidine hemicurcumin and Cisplatin: Synthesis, coordination chemistry, and in vitro activity assessment of a novel Pt(II) complex

Bridging pyrimidine hemicurcumin and Cisplatin: Synthesis, coordination chemistry, and in vitro activity assessment of a novel Pt(II) complex

  • J Inorg Biochem. 2024 Nov:260:112702. doi: 10.1016/j.jinorgbio.2024.112702.
Matteo Mari 1,  Matteo Boniburini 1,  Marianna Tosato 2,  Francesca Zanni 1,  Filippo Bonini 1,  Francesco Faglioni 1,  Laura Cuoghi 3,  Silvia Belluti 4,  Carol Imbriano 5,  Mattia Asti 6,  Erika Ferrari 7
Affiliations

Affiliations

  • 1 Department of Chemical and Geological Sciences, University of Modena and Reggio Emilia, via Campi, 103, 41125 Modena, Italy.
  • 2 Department of Chemical and Geological Sciences, University of Modena and Reggio Emilia, via Campi, 103, 41125 Modena, Italy; Radiopharmaceutical Chemistry Section, Nuclear Medicine Unit, Azienda USL-IRCCS Reggio Emilia, via Amendola 2, 42122 Reggio Emilia, Italy.
  • 3 Department of Life Sciences, University of Modena and Reggio Emilia, via Campi, 213/d, 41125 Modena, Italy. Electronic address: lacuoghi@unimore.it.
  • 4 Department of Life Sciences, University of Modena and Reggio Emilia, via Campi, 213/d, 41125 Modena, Italy. Electronic address: silvia.belluti@unimore.it.
  • 5 Department of Life Sciences, University of Modena and Reggio Emilia, via Campi, 213/d, 41125 Modena, Italy. Electronic address: carol.imbriano@unimore.it.
  • 6 Radiopharmaceutical Chemistry Section, Nuclear Medicine Unit, Azienda USL-IRCCS Reggio Emilia, via Amendola 2, 42122 Reggio Emilia, Italy. Electronic address: mattia.asti@ausl.re.it.
  • 7 Department of Chemical and Geological Sciences, University of Modena and Reggio Emilia, via Campi, 103, 41125 Modena, Italy. Electronic address: erika.ferrari@unimore.it.
PMID: 39163714 DOI: 10.1016/j.jinorgbio.2024.112702
Abstract

In the upcoming decades, the incidence and mortality rates of Cancer are expected to rise globally, with colorectal and prostate cancers among the most prevalent types. Despite advancements in molecular targeted therapy, platinum-based chemotherapies remain the cornerstone of treatment, especially for colorectal and prostate Cancer, with oxaliplatin and cisplatin being extremely effective due to their DNA-targeting capabilities. In our pursuit of new platinum-based chemotherapeutics that are potentially less toxic and more effective, we have explored the combination of the Pt-binding groups of the diaminocyclohexane ring used in oxaliplatin, with the stable amino-pyrimidine hemicurcumin moiety. This new derivative exhibit improved stability in physiological conditions and increased solubility in aqueous media, demonstrating promising effects on cell proliferation of both colorectal and prostate cells. We report herein the complete synthesis and chemical characterization in solution of the new derivative [(1R,2R)-N1-(3-(4-((E)-2-(2-Amino-6-methylpyrimidin-4-yl)vinyl)-2-methoxyphenoxy) propyl) cyclohexane-1,2-diamine] (MPYD). Our analysis includes an examination of its acid-base equilibria, speciation and stability in physiological conditions. The synthesis and in situ formation of Pt(II) complexes were investigated by nuclear magnetic resonance spectroscopy, while density functional theory calculations were employed to elucidate the chemical structure in solution. Results on the biological activity were obtained through cell viability assays on different colorectal and prostate cell lines (HCT116, HT29, PC3 and LNCaP).

Keywords

Amino-pyrimidine; Curcumin derivatives; Density Functional theory; Nuclear Magnetic Resonance; Oxaliplatin; Platinum-based drugs.

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