Isolation, structural elucidation, and cytotoxic activity investigation of novel styryl-lactone derivatives from Goniothalamus elegans : in vitro and in silico studies.

Two styryl-lactone derivatives (1 and 2) were isolated from the aerial parts of Goniothalamus elegans . Compound 1 is a newly discovered natural product, and compound 2 is reported in this plant for the first time. The absolute configuration of 1 was determined based on the ECD spectrum. The two styryl-lactone derivatives were tested for cytotoxicity activity against five cancer cell lines and human embryonic kidney cells. The newly discovered compound demonstrated potent cytotoxicity, with IC 50 values ranging from 2.05 to 3.96 μM. Computational methods were also applied to investigate the mechanism of the cytotoxic activity of the two compounds. Density functional theory and molecular mechanisms were used to assess the interaction between protein targets to compound 1 and 2, respectively, through the EGF/EGFR signaling pathway. The results indicated that 1 showed a strong binding affinity for two proteins EGFR and HER-2. Finally, ADMET predictions were used to validate the pharmacokinetics and toxicity of these compounds. The results showed that both compounds are likely to be absorbed in the gastrointestinal tract and penetrate the blood-brain barrier. Based on our findings, these compounds may have potential for further studies to be developed into active ingredients for cancer treatment.