2016
DOI: 10.1016/b978-0-444-63749-9.00002-5
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Natural Products as Lead Protein Kinase C Modulators for Cancer Therapy

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Cited by 15 publications
(14 citation statements)
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“…Considering the anti-CHIKV activity of PEs related to the present work, the structure–activity relationships have suggested the importance of the C-4 configuration, the influence of carbonyl at C-20 or C-7 and 6,7-epoxy function (which is spatially close to C-20) and the key role of acyl chains (See Section 1). These assumptions are in complete agreement with the pharmacophore model developed for phorbol-PKCs interactions [44,45,46,47,48].…”
Section: Protein Kinase C (Pkcs) As Targets Of Phorbol Esters For supporting
confidence: 77%
See 1 more Smart Citation
“…Considering the anti-CHIKV activity of PEs related to the present work, the structure–activity relationships have suggested the importance of the C-4 configuration, the influence of carbonyl at C-20 or C-7 and 6,7-epoxy function (which is spatially close to C-20) and the key role of acyl chains (See Section 1). These assumptions are in complete agreement with the pharmacophore model developed for phorbol-PKCs interactions [44,45,46,47,48].…”
Section: Protein Kinase C (Pkcs) As Targets Of Phorbol Esters For supporting
confidence: 77%
“…The interaction of phorbols with PKC is dependent on their substitution pattern and requires a combination of optimal hydrogen bonding and hydrophobic contacts for high potency. Phorbols bind to a cysteine-rich site replacing a molecule of water and establishing hydrogen bond interactions through the oxygen atoms bound to carbons C-3, C-4, and C-20 [48,49,50]. The hydrophobic acyl chains of phorbol esters allow complex formation with PKCs and their anchoring to the membrane [50].…”
Section: Protein Kinase C (Pkcs) As Targets Of Phorbol Esters For mentioning
confidence: 99%
“…There is evidence that this rapid action of ingenol mebutate is due to its dual action combining cytotoxic and immunomodulatory effects in which rapid lesion necrosis and antibody-dependent cellular cytotoxicity mediated by neutrophils occur [ 93 ]. The mechanism of action of ingenol mebutate is also partially related to the modulation of protein kinase C (PKC) to which it has a potent binding affinity by activating PKCδ and inhibiting PKCα [ 91 , 94 ]. In an in vitro assay, low isozyme selectivity was verified with a Ki ranging from 0.105–0.376 nM [ 95 ].…”
Section: Secondary Metabolites From Plants As Anticancer Agentsmentioning
confidence: 99%
“…Geminal methyl groups are also linked to the propenyl portion and the pyran ring A. Most bryostatins have an exocyclic methyl enoate in their B and C rings, others, instead, have a butenolide bound to the C-ring or glycals in place of hydroxyl moieties [98]. These compounds are produced by the proteobacterium Candidatus Endobugula sertula that lives in association with the marine bryozoan Bugula neritina.…”
Section: Macrolide Derivativesmentioning
confidence: 99%