Citation:

Structural characterization and biological properties of silver(I) tris(pyrazolyl)methane sulfonate, Almeida, J., Roma-Rodrigues Catarina, Mahmoud {Abdallah G. }, {Guedes da Silva} Fátima {M. C. }, Pombeiro {Armando J. L. }, Martins {Luísa M. D. R. S. }, Baptista {Pedro V. }, and Fernandes {Alexandra R. } , Journal of Inorganic Biochemistry, oct, Volume 199, (2019)

Abstract:

The water-soluble 1D helical coordination polymer [Ag(Tpms)]n (1) [Tpms = tris(pyrazolyl)methane sulfonate, −O3SC(pz)3; pz = pyrazolyl] was synthesized and fully characterized, its single-crystal X-ray diffraction analysis revealing the ligand acting as a bridging chelate N3-donor ligand. The antiproliferative potential of 1 was performed on two human tumour cell lines, A2780 and HCT116, and in normal fibroblasts, with a much higher effect in the former cell line (IC50 of 0.04 μM) as compared to the latter cell line and to normal fibroblasts. Compound 1 does not alter cell cycle progression but interferes with the adherence of A2780 cells triggering cell apoptosis. Apoptosis appears to occur via the extrinsic pathway (no changes in mitochondria membrane potential, reactive oxygen species (ROS) and pro-apoptotic (B-cell lymphoma 2 (BCL-2) associated protein (BAX))/anti-apoptotic (BCL-2) ratio) being this hypothesis also supported by the presence of silver mainly in the supernatants of A2780 cells. Results also indicated that cell death via autophagy was triggered. Proteomic analysis allowed us to confirm that compound 1 is able to induce a stress response in A2780 cells that is related with its antiproliferative activity and the trigger of apoptosis.

Notes:

This work was financed by national funds from the Foundation for Science and Technology FCT/MCTES ( UID/Multi/04378/2019 and UID/QUI/00100/2019 ), Portugal, and supported by the Applied Molecular Biosciences Unit- UCIBIO , and by the Centro de Química Estrutural (CQE at IST). AGM is thankful to the CATSUS doctoral program of FCT/MCTES for his PhD fellowship ( SFRH/BD/106006/2014 ). The authors acknowledge the Portuguese NMR Network (IST-UL Centre) for access to the NMR facility and the IST Node of the Portuguese Network of Mass-spectrometry for the ESI-MS measurements. CRR also acknowledges FCT/MCTES through SFRH/BPD/124612/2016. LMDRSM acknowledges FCT/MCTES through PTDC/QEQ-ERQ/1648/2014.