Synthesis, biological evaluation and SAR of 3-benzoates of ingenol for treatment of actinic keratosis and non-melanoma skin cancer

Autor:	Malene Bertelsen, Kristoffer Månsson, Thomas Högberg, Anke Soor, Morten Dahl Sørensen, Gunnar Grue-Sørensen, Karen Margrethe Engell, Martin Stahlhut, Per Vedsø, Xifu Liang
Rok vydání:	2014
Předmět:	Models Molecular Skin Neoplasms Stereochemistry medicine.medical_treatment Clinical Biochemistry Ingenol mebutate Pharmaceutical Science Antineoplastic Agents Benzoates Biochemistry Structure-Activity Relationship chemistry.chemical_compound Drug Discovery medicine Humans Protein Kinase Inhibitors Molecular Biology Cell Death Dose-Response Relationship Drug Molecular Structure Chemistry Organic Chemistry Actinic keratosis Biological activity medicine.disease Respiratory burst Keratosis Actinic Molecular Docking Simulation Protein Kinase C-delta Cytokine Cell Death Induction Cancer research Cytokines Molecular Medicine Diterpenes Drug Screening Assays Antitumor Skin cancer
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 24:54-60
ISSN:	0960-894X
Popis:	Ingenol 3-benzoates were investigated with respect to chemical stability, pro-inflammatory effects, cell death induction and PKCδ activation. A correlation between structure, chemical stability and biological activity was found and compared to ingenol mebutate (ingenol 3-angelate) used for field treatment of actinic keratosis. We also provided further support for involvement of PKCδ for induction of oxidative burst and cytokine release. Molecular modeling and dynamics calculations corroborated the essential interactions between key compounds and C1 domain of PKCδ.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4ef81444b0cd83146f287cf921961615 https://doi.org/10.1016/j.bmcl.2013.11.073 Zobrazit plný text záznamu Full Text from ScienceDirect