Molybdenum(II) allyl dicarbonyl complexes with 3-(2-pyridyl)pyrazole as potential CO-releasing molecules, antibacterial and antitumoral agents

Molybdenum-based CO-releasing molecules (CORMs) are attracting interest for biological and therapeutic applications. In this work two new complexes, [Mo(ηNunes and Calhorda (2015) 3 -C 3 H 5 )X(CO) 2 (Hpypz)] [X = Cl ( 1 ), Br ( 2 ); Hpypz = 3-(2-pyridyl)pyrazole] have been synthesized, characterized, and evaluated for their CO-release capacity, as well as antimicrobial and anticancer potential. The evaluation of the CO-release properties by the deoxymyoglobin‑carbonmonoxymyoglobin assay showed that the two complexes are comparably slow CO releasers in aqueous systems, showing a half-life of several hours, and sustained CO release over the course of the assay (6 h). Studies of biological activity were performed with complex 1 due to its better aqueous solubility. The antibacterial activity was investigated by determination of the minimum inhibitory and minimum bactericidal concentrations with the microdilution assay for gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and gram-negative Escherichia coli strains. Complex 1 displayed appreciable concentration-dependent bactericidal activity against both strains. The cytotoxicity of complex 1 was evaluated on human melanoma cells (A375) and immortalized nontumorigenic keratinocytes (HaCaT). Complex 1 exhibited selective cytotoxicity, significantly reducing the cell viability of A375 cells in a dose-dependent manner while having a lower effect on HaCaT cells, suggesting its antitumor potential against melanoma. In contrast, the precursor complex [Mo(ηNunes and Calhorda (2015) 3 -C 3 H 5 )Cl(CO) 2 (CH 3 CN) 2 ] showed reduced activity against A375 cells and higher toxicity toward HaCaT cells, highlighting the beneficial impact of the bidentate 3-(2-pyridyl)pyrazole ligand. • Preparation of the complexes [Mo( ηNunes and Calhorda (2015) 3 -C 3 H 5 )X(CO) 2 (3-(2-pyridyl)pyrazole)] (X = Cl, Br). • Myoglobin assay reveals a steady release of CO from the complexes in aqueous media. • The Cl complex ( 1 ) shows bactericidal activity against E. coli and S. aureus strains. • Cytotoxicity assays with melanoma (A375) and normal (HaCat keratinocytes) cell lines. • Complex 1 shows selective cytotoxicity and thus antitumor potential against melanoma.