Abstract
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.
Keywords:
Cell death induction; Cytokine release; Ingenol 3-benzoates; Molecular modeling; Oxidative burst; PKCδ activation.
Copyright © 2013 Elsevier Ltd. All rights reserved.
MeSH terms
-
Antineoplastic Agents / chemical synthesis
-
Antineoplastic Agents / chemistry
-
Antineoplastic Agents / pharmacology*
-
Benzoates / chemical synthesis
-
Benzoates / chemistry
-
Benzoates / pharmacology*
-
Cell Death / drug effects
-
Cytokines / metabolism
-
Diterpenes / chemical synthesis
-
Diterpenes / chemistry
-
Diterpenes / pharmacology*
-
Dose-Response Relationship, Drug
-
Drug Screening Assays, Antitumor
-
Humans
-
Keratosis, Actinic / drug therapy*
-
Keratosis, Actinic / metabolism
-
Keratosis, Actinic / pathology
-
Models, Molecular
-
Molecular Docking Simulation
-
Molecular Structure
-
Protein Kinase C-delta / antagonists & inhibitors
-
Protein Kinase C-delta / metabolism
-
Protein Kinase Inhibitors / chemical synthesis
-
Protein Kinase Inhibitors / chemistry
-
Protein Kinase Inhibitors / pharmacology*
-
Skin Neoplasms / drug therapy*
-
Skin Neoplasms / metabolism
-
Skin Neoplasms / pathology
-
Structure-Activity Relationship
Substances
-
Antineoplastic Agents
-
Benzoates
-
Cytokines
-
Diterpenes
-
Protein Kinase Inhibitors
-
Protein Kinase C-delta
-
ingenol