Synthesis of Tryptamine-Thiazolidin-4-one Derivatives and the Combined and Evaluation of their Biological Activity and Cytotoxicity.

Tryptamine, a monoamine alkaloid with an indole ring structure, is derived from the decarboxylation of the amino acid tryptophan, which is present in fungi, plants, and animals. Tryptamine analogues hold significant therapeutic potential due to their broad pharmacological activities, including roles as neurotransmitters and potential therapeutic agents for various diseases. Structural modifications of tryptamine enhance receptor selectivity and metabolic stability, improving therapeutic efficacy. These modifications are crucial for optimizing pharmacokinetic and pharmacodynamic properties, making the analogues more effective and safer for clinical use. In this study, novel tryptamine-thiazolidin-4-one (-) derivatives were synthesized via a one-pot three-component condensation reaction. The synthesized compounds are characterized by different spectroscopy techniques such as FT-IR, H NMR, C NMR, and HR-NMS. The synthesized compounds were subjected to binary QSAR disease models for bioactivity prediction and a target prediction model for target analysis. Potential targets were identified, and physics-based molecular simulations were conducted. Additionally, MM/GBSA binding free energy analysis was performed to calculate the average binding free energies of - compared to reference molecules. Our computational results indicated promising biological activities for these new compounds. To further investigate these activities, the compounds were tested using two different cancer cell lines: YKG-1 glioblastoma and SH-SY5Y neuroblastoma cells. The results confirmed the potential activities of these novel compounds. Notably, compounds and exhibited favorable activities compared to the control compounds 5-FU and Temozolomide. demonstrated an IC value of 20 nM against YKG-1 cells, while exhibited an IC value of 0.44 nM against SH-SY5Y cells.