SBIC ECR Symposium & Poster Presentation 21st International Conference on Biological Inorganic Chemistry 2025

Pt(II) organometallic complexes for the therapy of viral and parasitic tropical neglected diseases infections (#459)

Antônio Augusto de Oliveira Neto 1 , Gustavo C. Rodrigues 1 , Marcus S. A. Garcia 2 , Karen Minori 2 , Natasha M. Cassani 3 , Ana Laura C. Oliveira 3 , Bruna C. Sandim 3 , Ana Carolina G. Jardim 3 , Danilo C. Miguel 2 , Camilla Abbehausen 1
  1. Chemistry Institute, State University of Campinas, Campinas, Brazil
  2. Biology Institute, State University of Campinas, Campinas, São Paulo, Brazil
  3. Biology Institute, Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil

Our research group has been investigating metal-based compounds for the treatment of neglected diseases, such as arboviruses and leishmaniasis.1 In this work, Pt(II) NˆC phenylpyridine compounds were modified with phosphines generating the structures.(Figure 1) Among them 5 is a novel structure, characterized by spectroscopic techniques. The compounds are stable in DMSO and showed negligible chloride exchange reaction with N-acetyl-L-cysteine, demonstrating its stability with the thiol group. The partition coefficient (Log P) ranges 0.23 to 1.25, demonstrating their general lipophilicity. Complex 2 is the most lipophilic, 3 presents in the middle of the range and 5 is the most hydrophilic. Except by 5, the compounds presented interesting inhibition of Zika or Mayaro viruses (75 – 95 %) at non-cytotoxic concentrations, which is high (50 µM), as all the compounds are not cytotoxic to mammalian cells. Complex 3, seem to present the best lipophilic/hydrophilic balance of the series, and it was the only one to show activity against Leishmania (L.) amazonensis promastigotes. The EC50 of 3 is 3 μM and SI = 10. When evaluated the reduction of infection rates the compound presented 25% reduction. Interactions with BSA showed both dynamic and static quenching and a binding constant of 104 M-1, while the spectrophotometry of complexes interactions with DNA revealed hyperchromic or hypochromic effects depending on the complex, suggesting 3 and 4 can intercalate DNA. Except by 5, the complexes do not present intrinsic fluoresce in DMSO. Among the complexes, it was highlighted that Complex 3 exhibited fluorescence after interacting with histidine at Tris HCl pH 7.4 and acetate buffer pH 5.2. 2 (Figure 2)  Both the free and conjugated complexes exhibited significant fluorescence.

 

                                                                                                                                                             

                          67e47fa2c04cd-imagem_2025-03-26_193704341.png

                                                             Figure 1 : Structure of the five platinum complexes

67e47fa2c04cd-imagem_2025-03-26_193738148.png

Figure 2: Emission spectrum of complex 2, Histidine

and complex 2 + Histidine in the ratio 1:15 at pH 7,4 and 5,2.

  

  1. L. S. Oliveira et al., ChemBioChem, 25, 6, 1–11, 2024
  2. A. I. Solomatina et al., Bioconjug. Chem., 28, 2, 426–437, 2017.