The College of Pharmacy discussed the MSc thesis entitled “Molecular Modeling, Synthesis, Preliminary Antiproliferative Activity Evaluation of New Thiourea Derivatives” by the student Mazin Basim Ghadhban and the supervisor, Assistant Professor Dr. Ayad Abed Ali Al-Hamashi, at the Pharmaceutical Chemistry Department.
The study aimed to design ,evaluate novel thiourea-based compounds as potential compounds targeting sirtuin enzymes ,assess their preliminary cytotoxic activity against cancer cells. The study involved an in silico evaluation of the compounds using molecular docking, prediction of absorption, distribution, metabolism, excretion properties, molecular binding energy calculations, molecular dynamics simulations to evaluate their predicted binding characteristics toward the target proteins.
The study included structure-based computational design of a series of thiourea compounds, which were evaluated using molecular docking ,molecular dynamics simulations with the Schrödinger suite, with Selisistat used as a reference compound for comparison. Chemical synthesis of the selected compounds was then carried out, followed by purification of the resulting compounds using Combi Flash chromatography. Their chemical structures were confirmed and characterized using Fourier-transform infrared spectroscopy , nuclear magnetic resonance spectroscopy. The cytotoxic activity of the synthesized compounds was evaluated against the breast cancer cell line (MCF-7) , colon cancer cell line (SW480) using the MTT assay, with the results compared with those of the reference compound Selisistat.
The results showed that the synthesized compounds exhibited promising biological activity, with compound MB3 demonstrating the highest cytotoxic activity. Molecular docking studies revealed that compound MB3 exhibited high binding affinity toward SIRT2 , showed stronger predicted binding than the reference compound. Molecular dynamics simulations confirmed their structural and conformational stability within the active site of the enzyme.
The study recommended the synthesis of additional derivatives , expansion of the biological evaluation to include direct enzymatic assays to confirm the inhibitory mechanism against SIRT2, as well as cytotoxicity assessment , in vivo studies to determine safety levels. Further pharmacokinetic studies were recommended to evaluate the anticancer activity more comprehensively.
