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

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

doi:10.3389/fphar.2024.1344042

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

Front Pharmacol. 2024 Mar 4:15:1344042. doi: 10.3389/fphar.2024.1344042. eCollection 2024.

Authors

Endika Martín-Encinas¹, María Fuertes¹, Samuel Delgado-Hernández², Fernando García-Tellado², David Tejedor², Concepción Alonso¹

Affiliations

¹ Department of Organic Chemistry I, Faculty of Pharmacy and Lascaray Research Center (Lascaray Research Center), University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), Vitoria-Gasteiz, Spain.
² Instituto de Productos Naturales y Agrobiología, Consejo Superior de Investigaciones Científicas (Spanish National Research Council) Avda, La Laguna, Spain.

Abstract

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. In vitro cytotoxicity assessments revealed significant activity in SKOV3 ovarian carcinoma cells and A549 lung carcinoma cells. Structure-Activity Relationship (SAR) analysis indicated that the E 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 12E, with the E 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.

Keywords: cancer; chemotherapy; cyanomethyl vinyl ethers; cytotoxicity; tubulin inhibitors.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Financial support from Grants PID2021-122558OB-I00, PID2022-136566NB-I00 and PDC2022-133706-I00 funded by MCIN/AEI/10.13039/501100011033 and by the “European Union Next GenerationEU/PRTR” and by the Basque Government (GV, IT1701-22) is gratefully acknowledged.