AUTHOR=Martín-Encinas Endika , Fuertes María , Delgado-Hernández Samuel , García-Tellado Fernando , Tejedor David , Alonso Concepción 

TITLE=Synthesis, biological and computational evaluation of novel cyanomethyl vinyl ether derivatives

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1344042

DOI=10.3389/fphar.2024.1344042

ISSN=1663-9812

ABSTRACT=<p>This work explores the biological evaluation of novel cyanomethyl vinyl ether derivatives as antiproliferative agents. Tubulin, crucial to microtubule structure and function, is a target for cancer therapies. <italic>In vitro</italic> cytotoxicity assessments revealed significant activity in SKOV3 ovarian carcinoma cells and A549 lung carcinoma cells. Structure-Activity Relationship (SAR) analysis indicated that the <italic>E</italic> isomer and specific substitutions influenced the biological activity. Computational assays predicted favorable ADME properties, highlighting potential as anticancerous agents. Molecular docking studies demonstrated that compound <bold>12E</bold>, with the <italic>E</italic> geometry of the double bond and fused polyaromatic rings such as phenanthrene, has robust interaction with tubulin, suggesting enhanced stability due to diverse amino acid interactions. Comparative spatial distributions with colchicine further indicated potential mechanistic similarities.</p>