Crystal Structure and Anti-Proliferative and Mutagenic Evaluation of the Palladium(II) Complex of Deoxyalliin

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Candido, Tuany Zambroti ; Quintanilha, Mariana Mazzo ; Schimitd, Bianca Alves ; Simoni, Deborah de Alencar ; Nakahata, Douglas Hideki ; de Paiva, Raphael Enoque Ferraz ; Cerqueira, Igor Henrique ; Resende, Flavia Aparecida ; Carvalho, Joao Ernesto ; Ruiz, Ana Lucia Tasca Gois ; Lima, Carmen Silvia Passos ; Corbi, Pedro Paulo

• Document type: Journal article
• Source: INORGANICS; v. 12, n. 7, p. 11-pg., 2024-07-01.

Abstract

Platinum(II) and palladium(II) complexes have been investigated as potential anticancer drugs since the serendipitous discovery of the antineoplastic activities of cisplatin in the 1960s. Skin cancer is considered the most common malignant neoplasm that affects humans, and melanoma is the most lethal type of skin cancer. Surgical excision is the main form of treatment, which also may include radiotherapy, systemic chemotherapy, and immunotherapy. In this work, new insights concerning the structural characterization and in vitro anti-proliferative activity of the palladium(II) complex with the amino acid deoxyalliin (Pd-sac) against a panel of thirteen human tumor cells, with emphasis on skin cancer cell lines, are presented. The composition of the complex was confirmed by elemental analysis as [Pd(C6H10NO2S)(2)]. The structure of the complex was elucidated for the first time by a single-crystal X-ray diffraction technique. Each deoxyalliin molecule coordinates in a bidentate N,S-mode to palladium(II) in a trans-configuration analogous to the platinum(II) deoxyalliin complex early reported. As the main result, the Pd-sac complex showed a selective anti-proliferative activity against melanoma (UACC-62, TGI = 63.5 mu M), while both deoxyalliin and K2PdCl4 were inactive against all cell lines. Moreover, Pd-sac did not affect the proliferation of non-tumorigenic keratinocytes (HaCaT, TGI > 586 mu M) and was non-mutagenic in the Ames assay. The results open new perspectives for in vivo studies concerning the application of the Pd-sac complex in the treatment of melanoma. (AU)

• FAPESP's process: 21/10265-8 - Cancer Theranostics Innovation Center (CancerThera)
• Grantee: Carmino Antonio de Souza
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 18/09860-6 - Synthesis, characterization and studies of the antibacterial activities of Ag(I), Cu(II) and Pt(II) complexes with sulfamethazine
• Grantee: Bianca Alves Schimitd
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 16/07729-4 - Metal complex from golden, palladium and silver in the treatment of skin squamous cell carcinoma
• Grantee: Tuany Zambroti Cândido
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/12062-4 - Synthesis, characterization and studies of interaction with biomolecules of metal complexes containing biologically active ligands: a strategy in the preparation of new agents with antibacterial and antiviral activities
• Grantee: Pedro Paulo Corbi
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/09856-9 - New studies of synthesis, characterization and antitumor activity of Pd(II) and Pt(II) complexes with S-allyl-L-cysteine
• Grantee: Mariana Mazzo Quintanilha
• Support Opportunities: Scholarships in Brazil - Scientific Initiation