Synthesis, characterization, in vitro and in silico assessment of novel diclofenac derivative metal complexes

• Published in: Journal of molecular structure Vol. 1318; p. 139191
• Main Authors: Abbas, A.M., Salem, H.A., Orabi, A.S.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15-12-2024
• Subjects: Anti-inflammatory; Antitumor; Diclofenac antitumor; Hydrazone; In silico; In vitro; In silico; Hydrazone; In vitro; Anti-inflammatory; Diclofenac antitumor; Antitumor
• ISSN: 0022-2860
• DOI: 10.1016/j.molstruc.2024.139191

•Synthesis of salicylaldehyde-diclofenac hydrazone and its metal complexes.•Characterization of compounds using NMR, FTIR, and UV–Vis, XRD.•Evaluation of anti-inflammatory and antitumor activities.•Docking studies with COX-1, COX-2, HepG-2, and MCF-7 receptors.•Assessment of physicochemical properties, pharmacokinetics, and drug-likeness using computational methods.
A novel hydrazone ligand was synthesized by condensing diclofenac hydrazide with salicylaldehyde. This ligand was then used to create complexes with cobalt(II), nickel(II), copper(II), gadolinium(III), lanthanum(III), and silver(I). Structural characterization of these compounds was achieved through various techniques, including nuclear magnetic resonance spectroscopy, infrared spectroscopy, ultraviolet-visible spectroscopy, mass spectrometry, elemental analysis, thermal analysis, magnetic susceptibility measurements, electron spin resonance spectroscopy, X-ray diffraction, and conductivity measurements. The inhibitory effects of the synthesized compounds on cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes, critical targets for anti-inflammatory drugs, were assessed. Notably, the cobalt(II) and silver(I) complexes exhibited high selectivity for inhibiting COX-2, with selectivity indices of 118.75 and 105.00, respectively. The antitumor potential of the compounds was evaluated against MCF-7 (breast cancer) and HepG-2 (liver cancer) cell lines. The copper(II) and gadolinium(III) complexes demonstrated the highest efficacy, significantly inhibiting the growth of both cancer cell lines with half-maximal inhibitory concentration (IC50) values as low as 0.37 µM and 0.58 µM (MCF-7) and 0.35 µM and 0.67 µM (HepG-2), respectively. These complexes outperformed the original ligand in inhibiting cancer cell growth. In silico studies, using the SwissADME web tool and AutoDocke Vina, corroborated the experimental findings and provided insights into the compounds' physicochemical properties, pharmacokinetics, drug-likeness, and potential binding interactions with COX-1, COX-2, and the target proteins in the cancer cell lines.
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