Novel thiourea derivative compounds: Thermal behavior, biological evaluation, Hirshfeld surfaces and frontier orbitals analyses, in silico ADMET profiling and molecular docking studies

This work reports synthesis and structural characterization of N-(allylcarbamothioyl)-2-chlorobenzamide (HL1, C11H11ClN2OS) and N-(allylcarbamothioyl)-2-methylbenzamide (HL2, C12H14N2OS). Structural char-acterization studies were made via elemental analysis, FT-IR, 1H NMR and single crystal XRD techniques. Thermal behavior of the synthesized compounds were investigated via TG/DTA. The cell similarity cal-culation was made. The Is value for HL1 and HL2 was found to be 86.9%. The HL1 and HL2 compounds were found to be thermally stable upto 136 and 132 degrees C, respectively. Anticancer activity of the com-pounds against MCF-7 breast cancer cells was studied via cell viability test and MTT. The role and the effect of different functional groups present in the compounds on anticancer activity were investigated. The IC50 values were found to be in the range 2.59 - 7.09 mu mol.L-1. The HL1 compound showed good antitumor activity at 2.59 mu mol.L1 at 48 h. The Hirshfeld surfaces analyses of the compounds were made. The HOMO-LUMO energy levels of HL1 and HL2 were calculated. The compounds were thoroughly in-vestigated in silico for their ADMET characteristics. The physicochemical, pharmacological, and ADMET characteristics of HL1 and HL2 were investigated together with drug similarity metrics. The compounds were observed to have good drug-like property. Furthermore, molecular docking experiments were car-ried out to evaluate the interactions between the compoundssynthesized in this study and BRAF (V600E-protein kinase). The acquired results revealed that the synthesized compounds had high binding affinity and inhibitory effect on the BRAF (V600E) protein kinase. The synthesized compounds can be considered potent anticancer agents, according to the data obtained using both in vitro and in silico techniques.(c) 2023 Elsevier B.V. All rights reserved.