Akademik Veri Yönetim Sistemi
Bioorganic Chemistry, cilt.169, 2026 (SCI-Expanded, Scopus)
Thiourea derivatives possess a wide spectrum of biological activities and play a crucial role in drug design due to their anticancer, antimicrobial, antiviral, and enzyme inhibitory properties. In this study, seven novel substituted phenethylamine-based aroyl thiourea derivatives (23–29) with previously unreported structures were synthesized, and their biological activities were comprehensively evaluated. In the synthesis step, various substituted phenethylamines were reacted with 4-methoxyphenyl chloroformate in the presence of potassium thiocyanate, and the resulting compounds were characterized using FT-IR and NMR spectroscopic techniques. Antibacterial assays revealed that compounds 25, 26 , and 28 exhibited strong antibacterial activity against multidrug-resistant pathogenic strains, with MIC values ranging from 6.25 to 100 μM. Notably, compounds 25, 27, and 28 displayed the most potent efficacy with MIC values as low as 6.25 μM. Antioxidant analyses performed using the CUPRAC and DPPH methods demonstrated that electron-donating groups (compound 27) enhanced reducing capacity, whereas electron-withdrawing groups (compound 28) limited this effect. In anticancer evaluations, compounds 27 and 28 exhibited significant antiproliferative activity against A549 cells with IC50 values of 124.4 μM and 106.1 μM, respectively, while displaying minimal cytotoxicity toward normal HDF-1 cells. In silico analyses indicated that all synthesized compounds complied with Lipinski's rule of five and possessed favorable bioavailability. Molecular docking studies further confirmed these findings, revealing strong binding affinities ranging from −5.3 to −9.2 kcal/mol. Specifically, compound 26 showed the highest binding potential with a score of −9.2 kcal/mol against the target protein (PDB ID: 5AA4). These findings suggest that the synthesized aroyl thiourea derivatives serve as promising multifunctional biological agent candidates.