Synthesis of Tryptamine-Thiazolidin-4-one\nDerivatives\nand the Combined <i>In Silico</i> and <i>In Vitro</i> Evaluation of their Biological Activity and Cytotoxicity

Tryptamine, a monoamine alkaloid with an indole ring\nstructure,\nis derived from the decarboxylation of the amino acid tryptophan,\nwhich is present in fungi, plants, and animals. Tryptamine analogues\nhold significant therapeutic potential due to their broad pharmacological\nactivities, including roles as neurotransmitters and potential therapeutic\nagents for various diseases. Structural modifications of tryptamine\nenhance receptor selectivity and metabolic stability, improving therapeutic\nefficacy. These modifications are crucial for optimizing pharmacokinetic\nand pharmacodynamic properties, making the analogues more effective\nand safer for clinical use. In this study, novel tryptamine-thiazolidin-4-one\n(<b>YS1</b>-<b>12</b>) derivatives were synthesized via\na one-pot three-component condensation reaction. The synthesized compounds\nare characterized by different spectroscopy techniques such as FT-IR, <sup>1</sup>H NMR, <sup>13</sup>C NMR, and HR-NMS. The synthesized compounds\nwere subjected to binary QSAR disease models for bioactivity prediction\nand a target prediction model for target analysis. Potential targets\nwere identified, and physics-based molecular simulations were conducted.\nAdditionally, MM/GBSA binding free energy analysis was performed to\ncalculate the average binding free energies of <b>YS1</b>-<b>12</b> compared to reference molecules. Our computational results\nindicated promising biological activities for these new compounds.\nTo further investigate these activities, the compounds were tested <i>in vitro</i> using two different cancer cell lines: YKG-1 glioblastoma\nand SH-SY5Y neuroblastoma cells. The results confirmed the potential\nactivities of these novel compounds. Notably, compounds <b>YS4</b> and <b>YS10</b> exhibited favorable activities compared to\nthe control compounds 5-FU and Temozolomide. <b>YS4</b> demonstrated\nan IC<sub>50</sub> value of 20 nM against YKG-1 cells, while <b>YS10</b> exhibited an IC<sub>50</sub> value of 0.44 nM against\nSH-SY5Y cells.