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Polygodial and Ophiobolin A Analogues for Covalent Crosslinking of Anticancer Targets

In a search of small molecules active against apoptosis-resistant cancer cells, including glioma, melanoma, and non-small cell lung cancer, we previously prepared α,β- and γ,δ-unsaturated ester analogues of polygodial and ophiobolin A, compounds capable of pyrrolylation of primary amines and demonst...

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Detalles Bibliográficos
Autores principales: Maslivetc, Vladimir, Laguera, Breana, Chandra, Sunena, Dasari, Ramesh, Olivier, Wesley J., Smith, Jason A., Bissember, Alex C., Masi, Marco, Evidente, Antonio, Mathieu, Veronique, Kornienko, Alexander
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8537666/
https://www.ncbi.nlm.nih.gov/pubmed/34681916
http://dx.doi.org/10.3390/ijms222011256
Descripción
Sumario:In a search of small molecules active against apoptosis-resistant cancer cells, including glioma, melanoma, and non-small cell lung cancer, we previously prepared α,β- and γ,δ-unsaturated ester analogues of polygodial and ophiobolin A, compounds capable of pyrrolylation of primary amines and demonstrating double-digit micromolar antiproliferative potencies in cancer cells. In the current work, we synthesized dimeric and trimeric variants of such compounds in an effort to discover compounds that could crosslink biological primary amine containing targets. We showed that such compounds retain the pyrrolylation ability and possess enhanced single-digit micromolar potencies toward apoptosis-resistant cancer cells. Target identification studies of these interesting compounds are underway.