Synthesis and evaluation of anticancer and anti-invasive properties of 3-aminowithaferin A and its imine congeners.

AIM: Synthesisof 3-aminowithaferin A and its imine congeners to identify promising lead molecules for future development as anti-cancer agents. MATERIALS AND METHODS: 3-Aminowithaferin A was synthesized through aza-Michael addition using liquid ammonia as a nucleophile. In order to obtain imine congeners various aldehydes were allowed to undergo addition-elimination with 3-aminowithaferin A. All the newly synthesized compounds were screened for their cytotoxicity against eight cancers and one normal cell line using MTT assay. RESULTS AND CONCLUSION: One of the imine analogs, referred to as compound 13, exhibited significant antiproliferative and anti-metastatic properties across various cell lines, particularly in triple-negative breast cancer lines, with an IC50 value ranging from 507 nM to 2.475 µM. Compound 13 effectively inhibited the formation of invadopodia and filopodia, underscoring its anti-invasive properties. Additionally, immunoblotting studies demonstrated a consistent decrease in the expression of various epithelial-to-mesenchymal transition (EMT) markers in the presence of compound 13, further confirming its anti-metastatic properties.