Manganese(i) based NN∩SS bis-chelated homo-binuclear metallacycles: synthesis, spectral, crystallographic, anticancer potential and molecular docking studies

Abstract

Reaction of Mn₂(CO)₁₀, dithiooxamide ligand [H₂L = N,N′-dibutyldithioxamide (dbdto) and N,N′-diphenethyldithioxamide (dpedto)], and flexible bidentate linkers [L′ = 1,2-bis(4-pyridyl)ethane (bpe), 1,3-bis(4-pyridyl)propane (bpp)] produced binuclear metallacyclic compounds [(CO)₃Mn(µ-η⁴-L)(µ-L′)Mn(CO)₃] (1–4) under ambient reaction conditions. Compounds 1–4 were characterized by elemental analysis, FT-IR, UV-Vis, and NMR spectroscopy, and the formation of dinuclear metallacycles 1–4 was confirmed by high-resolution ESI mass spectrometry. The molecular structure of compound 4 was determined by single-crystal X-ray crystallography, revealing a dinuclear horse-stirrup like framework. The anticancer properties of the metallacycles were investigated in vitro on two different cancer cell lines, osteosarcoma (MG-63) and breast cancer (MCF-7), and normal cells (HEK-293). Compounds 2 and 4 showed moderate cytotoxicity toward MG-63 and MCF-7 cells, with IC₅₀ values of 65.58 ± 1.54 and 151.19 ± 1.66 µg mL⁻¹ for compound 2 and 78.58 ± 3.83 and 125.42 ± 10.77 µg mL⁻¹ for compound 4, respectively, while showing lower toxicity toward HEK-293 cells. Furthermore, qualitative in silico docking studies of compound 4 were performed with cancer related proteins, epidermal growth factor receptor tyrosine kinase (EGFRK, PDB ID: 1M17) and human matrix metalloproteinase-9 (MMP-9, PDB ID: 1L6J) to explore possible binding interactions.