In vitro and in silico studies of a di-copper cyclam complex for anticancer application: functionalization, cytotoxicity, ADMET profile and molecular docking as a VEGFR1 inhibitor

Abstract

Single crystals of the dinuclear cyclam complex (1, 4, 8, 11-tetraazacyclotetradecane)-copper (ii) tetrachlorocuprate {[Cu(14-ane)]CuCl₄} (1) were prepared by soft chemistry. The powder, resulting from their grinding, was characterized by FTIR spectroscopy and functionalized using silica support materials MSN and halloysite H. The in vitro studies conducted on (1) formulated with MSN or halloysite H against kidney epithelial cell line (HK2) and renal cancer cell (RCC) lines (Caki-2, TW, LN78) demonstrated significant antiproliferative effects for both renal cell types. An increase in the apoptosis levels in the RCC lines underscoring the potential as an anticancer therapeutic agent was observed. These findings were corroborated by an in silico analysis aimed at exploring the ADMET profile of (1), indicating favorable aqueous solubility, brain penetration and druglikeness properties akin to FDA-approved VEGFR inhibitors such as sorafenib and cabozantinib. To gain deeper insights into the anticancer behavior of (1), molecular docking simulations against the vascular endothelial growth factor receptor VEGFR1 (PDB entry code 3HNG) were conducted. The evaluation of the interacting modes and binding sites in the 3HNG-(1) target–ligand complex revealed diverse hydrogen-bonding interactions within the receptor’s binding pocket, suggesting a promising inhibition potential of (1) against VEGFR1.