Acyl Derivatives of Eudesmanolides To Boost their Bioactivity: An Explanation of Behavior in the Cell Membrane Using a Molecular Dynamics Approach
| Autor: | Francisco A. Macías, José M. G. Molinillo, Jesús G. Zorrilla, Rosa M. Varela, Alexandra G. Durán, Francisco J R Mejías, Manuel M. Valdivia |
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| Rok vydání: | 2021 |
| Předmět: |
Apoptosis
Molecular Dynamics Simulation Sesquiterpene 01 natural sciences Biochemistry Cell membrane Structure-Activity Relationship chemistry.chemical_compound Molecular dynamics Drug Discovery medicine Humans General Pharmacology Toxicology and Pharmaceutics Cell Proliferation Pharmacology Natural product Molecular Structure 010405 organic chemistry Aryl Cell Membrane Organic Chemistry Antineoplastic Agents Phytogenic Combinatorial chemistry 0104 chemical sciences 010404 medicinal & biomolecular chemistry HEK293 Cells medicine.anatomical_structure chemistry Cell culture Lipophilicity Molecular Medicine Selectivity Sesquiterpenes HeLa Cells |
| Zdroj: | ChemMedChem. 16:1297-1307 |
| ISSN: | 1860-7187 1860-7179 |
| DOI: | 10.1002/cmdc.202000783 |
| Popis: | Semisynthetic analogs of natural products provide an important approach to obtain safer and more active drugs and they can also have enhanced physicochemical properties such as persistence, cross-membrane processes and bioactivity. Acyl derivatives of different natural product families, from sesquiterpene lactones to benzoxazinoids, have been synthesized and tested in our laboratories. These compounds were evaluated against tumoral and nontumoral cell lines to identify selective derivatives with a reduced negative impact upon application. The mode of action of these compounds was analyzed by anti-caspase-3 assays and molecular dynamics simulations with cell membrane re-creation were also carried out. Aryl derivatives of eudesmanolide stand out from the other compounds and are better than current anticancer drugs such as etoposide in terms of selectivity and activity. Computational studies provide evidence that lipophilicity plays a key role and the 4-fluorobenzoyl derivative can pass easily through the cell membrane. |
| Databáze: | OpenAIRE |
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