Future medicinal chemistry · 2025
Synthesis and evaluation of anticancer and anti-invasive properties of 3-aminowithaferin A and its imine congeners.
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Mir Shabir Ahmad, Amin Tanzeeba, Hussain Gulzar, Mir Khalid Bashir, Kaur Gursimar, Firdous Sameera, Goswami Anindya, Yousuf Syed Khalid
Аннотация
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.
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.