Synthesis of new thiourea derivatives and metal complexes: Thermal behavior, biological evaluation, in silico ADMET profiling and molecular docking studies

Abstract

In this work, N-((5-bromopyridin-2-yl)carbamothioyl)-2-chlorobenzamide (HL1) and N-((5-bromopyridin -2-yl)carbamothioyl)furan-2-carboxamide (HL2) and its Cu, Ni and Co metal complexes were prepared. Elemental analysis, FT-IR, UV–vis.,1H NMR, single crystal XRD techniques, magnetic susceptibility and DTA/TG analysis were used for structural characterization. The thermal behaviors of the HL1, HL2 and its complexes were investigated. HL1 and HL2 ligands were thermally stable up to 119 and 134 °C, respectively. After the structures of the compounds were characterized, anticancer activity studies were performed, and the effects of different groups on the activity were investigated. Cell viability test MTT was made to determine anticancer activities against MCF-7 breast cancer cells. IC50 values for MCF-7 cells were in the range of 2.07 µM – 21.25 µM. The NiL12 complex showed better antitumor activity when at 2.07 µM concentration in 24 h. For their ADMET properties, ligands and metal complexes have been comprehensively studied in silico. Notably, when the physicochemical, pharmacological and ADMET properties of ligands HL1 and HL2 were evaluated together with drug similarity parameters, good drug-like behavior of the compounds was revealed. In addition, molecular docking studies were performed to assess the binding interactions between ligands and complex compounds and BRAF (V600E -protein kinase). According to the obtained results, it was confirmed that all synthesized compounds exhibited high binding affinity and had an inhibitory effect against BRAF (V600E) protein kinase. The results obtained with both in vitro and in silico approaches have shown that the synthesized compounds can be evaluated as potent anticancer agents.