Synthesis, Characterization, and Cytotoxic Activity Properties of Some Novel Purine Derivatives

OpenAlex · English

ABSTRACT This study reports the synthesis of nine new compounds with purine scaffolds. It thoroughly analyzes them using a variety of spectroscopic methods, including high‐resolution mass spectrometry (HR‐MS), proton nuclear magnetic resonance (¹H NMR), attached proton test nuclear magnetic resonance (¹³C APT NMR), and fourier‐transform infrared spectroscopy (FT‐IR). The in vitro cytotoxic potential of these compounds was examined using two cancer cell lines: MDA‐MB‐231, a model of triple‐negative breast cancer, and HepG2, a model of liver carcinoma. Furthermore, compounds were tested in a normal mouse fibroblast cell line (L929). Biological screening revealed that two of the synthesized molecules, ethyl 2‐(2‐(2‐(9 H ‐purin‐6‐yl)hydrazineylidene)‐3‐(4‐methylphenyl)‐4‐oxothiazolidin‐5‐ylidene)acetate (4b) and ethyl 2‐(2‐(2‐(9 H ‐purin‐6‐yl)hydrazineylidene)‐3‐(4‐nitrophenyl)‐4‐oxothiazolidin‐5‐ylidene)acetate (4c) exerted cytotoxic effects with IC 50 values of 137.10 ± 6.46 and 130.70 ± 5.81 µM against the HepG2 cell line, respectively. At the same time, seven compounds (2b, 3a, 3b, 3c, 4a, 4b, and 4c) exhibited cytotoxic activity against MDA‐MB‐231 cells with IC 50 values of 197.40 ± 5.84, 161.90 ± 4.17, 66.33 ± 2.53, 122.10 ± 3.87, 159.80 ± 4.92, 138.10 ± 3.75, and 131.50 ± 2.46 µM, respectively. Caspase‐3 activity assays were performed on the MDA‐MB‐231 cell line, which exhibited activity, and fluorescence imaging studies were also conducted. To elucidate potential molecular targets, in silico docking analyses were performed, indicating 15‐lipoxygenase (15‐LOX) as a likely enzymatic target. Among the evaluated molecules, compound 4b demonstrated superior binding affinity toward 15‐LOX, even exceeding that of the co‐crystallized reference inhibitor. The stability of the 4b–enzyme complex was further supported by molecular dynamics (MD) simulations, which showed an improved interaction profile compared to the original inhibitor–enzyme complex.