Computer-aided drug design has emerged as an efficient tool of developing candidate drugs for the treatment of many diseases. The thiourea derivatives represent one of the most promising classes of compounds that exhibit various biological properties. The aim of this mini literature review was to analyze the molecular fitting of synthesized thiourea derivatives into the actives sites of COX-1, COX-2 and 5-LOX. Lipinski’s rule of 5 is widely used in rational drug design to predict drug similarity and druglikeness. Among selected compounds with available druglikeness data, all molecules meet criteria for Lipinski’s rule except compounds 2-4 and 41-46. In silico molecular docking analysis were performed in Molecular Operating Environment, OpenEye, AutoDock Tools and AutoDock Vina to explore the binding modes of these compounds into the active sites of target proteins. Within the molecular docking analysis, the interactions of key amino acid residues of enzyme's active sites involved in ligand-protein interactions were investigated. Based on the results highlighted in this review we can conclude that certain structural features of thiourea derivatives contribute to high binding potential to interact with active sites of COX-1, COX-2 and 5-LOX. It was observed that insertion of carboxyl functional group to the parent compounds increased interaction strength due to formation of additional hydrogen bonds. On the other hand, introduction of pi-reached heterocycles increased the number of hydrophobic interactions that leads to higher binding affinity towards target proteins.
M. Nikolić, M. Mijajlović, N. Nedeljković, “Anti-Inflammatory Screening of Thiourea Derivatives Based on Molecular Docking Studies,” in Sinteza 2022 - International Scientific Conference on Information Technology and Data Related Research, Belgrade, Singidunum University, Serbia, 2022, pp. 365-372. doi:10.15308/Sinteza-2022-365-372
Nikolić, M., Mijajlović, M., Nedeljković, N. (2022). Anti-Inflammatory Screening of Thiourea Derivatives Based on Molecular Docking Studies. Paper presented at Sinteza 2022 - International Scientific Conference on Information Technology and Data Related Research. doi:10.15308/Sinteza-2022-365-372