Synthesis, Cytotoxic Activity, mRNA Expression, Total Oxidant and Antioxidant Status, and Molecular Modeling Studies of Novel Schiff Base–Thiosemicarbazone Hybrids

Several new Schiff‐based compounds were synthesized, and their chemical structures were confirmed usingFT‐IR, 1 H‐NMR, 13 C‐NMR, and HRMS. The compounds were tested in the prostate cancer cell line (PC3) for 72 h. The results demonstrated that compounds NZ10 , NZ9 , NZ7 , and NZ4 had high cytotoxic effects on the PC3 cell line with IC 50 values of 10.54, 14.58, 15.85, and 16.48 µM, respectively. The modulator roles of selected compounds on apoptotic signaling were tested by their effect on mRNA expression levels of BAX , BID , BCL2 , and BCL‐xL using RT‐qPCR. Furthermore, the effects on oxidative stress levels were examined by measuring total oxidant and antioxidant levels in cells. The results revealed that selected compounds significantly upregulated pro‐apoptotic BAX and BID , whereas they downregulated anti‐apoptotic BCL2 and BCL‐xL levels. Besides, compounds were found to significantly increase the oxidative status in cells. The binding potential of relatively active compounds to BCL‐2 was assessed through molecular docking and molecular dynamics (MD) simulations. The docking study demonstrated that compounds had binding potential to the structure but were weaker than the standard drug, venetoclax. MD simulation analysis showed that complexes of the compounds with higher affinity formed stable complexes with the structure.