Synthesis, In silico Study and Cytotoxicity Evaluation of Some Newly Synthesized Stilbene Derivatives

Abstract

A series of 12 stilbene derivatives (23-34) were synthesized by reacting benzyl-triphenylphosphonium chlorides (9-14) and hydrochloride salt of 3,5-disubstituted-4-hydroxybenzaldehydes (21-22). The synthesized molecules were tested against the human breast cancer cell line MCF7 by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in 10% Dulbecco’s modified Eagle Medium (DMEM). Compound 23 exhibited significant cytotoxicity, with 1.11% viability at a concentration of 200 µM, compared to the reference standard resveratrol (15.14%) and 5-fluorouracil (51.86%). All the synthesized derivatives demonstrated equipotency to 5-fluorouracil (5-FU) at all the tested concentrations. The docking study was conducted on the tyrosine-protein kinase/Janus Kinase 2(JAK2) receptor using Autodock Vina. The results of the docking study suggest that, with the exception of compounds 29 (-6.7 kcal/mol) and 32 (-7.1 kcal/mol), most of the synthesized derivatives have exhibited glide scores greater than the standard resveratrol (-7.8 kcal/mol). This implies that these compounds 23-34 have a strong binding affinity to the JAK2 receptor, which is relevant in the context of cancer research, as JAK2 is associated with various signaling pathways involved in cell proliferation and survival.