Mononuclear Copper(I) Complexes With Acylthiourea Ligands as Potential Anticancer Agents Against Pancreatic Cancer: Synthesis, Structural Characterization, DFT Calculations, and Docking Studies

ABSTRACT In this study, two acylthiourea ligands ( L1 and L2 ) were synthesized and coordinated to Cu(I) to afford mononuclear complexes 1 and 2 featuring sulfur‐bound ligands that generate a three‐coordinate Cu(S) 2 Br core. Spectroscopic analyses (FT‐IR, UV–Vis, 1 H and 13 C NMR) together with ESI‐MS confirmed successful coordination and analogous coordination environments for both complexes. Single‐crystal X‐ray diffraction (SCXRD) of complex 1 revealed a distorted trigonal‐planar geometry with strong Cu‐S interactions and additional stabilization through intermolecular C‐H···Br and π···π contacts. Density functional theory (DFT‐D3) calculations indicated metal‐centered HOMO character, ligand‐centered LUMO distribution, and reduced HOMO‐LUMO gaps upon coordination, with complex 2 exhibiting higher softness and electrophilicity consistent with enhanced reactivity. Molecular docking studies against PDGFRA predicted stronger binding affinity for the copper complexes than for the free ligands, with complex 2 exhibiting the most favorable interaction profile. In vitro cytotoxicity assessed by the MTT assay against pancreatic cancer cell lines (PANC‐1, MIA PaCa‐2, and AsPC‐1) showed that complex 2 exhibits superior growth inhibition compared with complex 1 and cisplatin, while maintaining better selectivity toward normal cells, with IC 50 values of 16.5 ± 0.1 μM for PANC‐1 and MIA PaCa‐2 and 8.1 ± 0.4 μM for AsPC‐1. Collectively, the structural, computational, and biological findings highlight Cu(I)‐acylthiourea complexes as promising candidates for further development as anticancer agents.