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

Authors :: Grue-Sørensen G
Liang X
Månsson K
Vedsø P
Dahl Sørensen M
Soor A
Stahlhut M
Bertelsen M
Engell KM
Högberg T
Source :: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2014 Jan 01; Vol. 24 (1), pp. 54-60. Date of Electronic Publication: 2013 Dec 04.
Publication Year :: 2014
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.<br /> (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Subjects :: Antineoplastic Agents chemical synthesis
Antineoplastic Agents chemistry
Benzoates chemical synthesis
Benzoates chemistry
Cell Death drug effects
Cytokines metabolism
Diterpenes chemical synthesis
Diterpenes chemistry
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
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
Skin Neoplasms metabolism
Skin Neoplasms pathology
Structure-Activity Relationship
Antineoplastic Agents pharmacology
Benzoates pharmacology
Diterpenes pharmacology
Keratosis, Actinic drug therapy
Protein Kinase Inhibitors pharmacology
Skin Neoplasms drug therapy

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