Novel Phenethylamine-Based Aroyl Thiourea Derivatives: Design, Synthesis, and Multibiological Evaluation

Drug discovery remains a major global challenge despite significant advances in science and technology that have accelerated drug development efforts. To address this need, numerous studies have focused on designing novel drug molecules with improved efficacy, low toxicity, and cost-effectiveness. Thioureas and their derivatives play a crucial role in medicinal chemistry due to their diverse biological properties, including anticancer, antioxidant, antimicrobial, and anti-inflammatory effects. In this study, seven aroyl thiourea compounds based on substituted phenethylamine were synthesized. Their anticancer, antioxidant, and antibacterial activities were evaluated along with their physicochemical and drug-like properties through in silico analysis using the SwissADME software. Among the synthesized compounds, compound 14, a novel aroyl thiourea derivative, exhibited higher antiproliferative activity than the positive control methotrexate (MTX) against A549 cells, whereas the compounds generally showed moderate antiproliferative effects in HeLa cells. None of the compounds showed cytotoxic effects on the healthy HDF-1 cell lines. Antioxidant activities were determined using CUPRAC and DPPH assays, revealing that compound 10 had the most notable antioxidant capacity in both tests. Additionally, compounds 12 and 15 demonstrated notable antibacterial activity against the bacterial isolates. Overall, in silico results indicated that all synthesized aroyl thiourea compounds possess favorable physicochemical characteristics, and it has been determined that they may have potential as medicines.