Natural Products as Lead Protein Kinase C Modulators for Cancer Therapy

Matias, Diogo; Bessa, Cláudia; Simões, M. Fátima; Reis, Catarina Pinto; Rijo, Patrícia

doi:10.1016/b978-0-444-63749-9.00002-5

Cited by 15 publications

(14 citation statements)

References 154 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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%

See 1 more Smart Citation

Macrocyclic Diterpenoids from Euphorbiaceae as A Source of Potent and Selective Inhibitors of Chikungunya Virus Replication

Rémy

Litaudon

2019

Molecules

View full text Add to dashboard Cite

Macrocyclic diterpenoids produced by plants of the Euphorbiaceae family are of considerable interest due to their high structural diversity; and their therapeutically relevant biological properties. Over the last decade many studies have reported the ability of macrocyclic diterpenoids to inhibit in cellulo the cytopathic effect induced by the chikungunya virus. This review; which covers the years 2011 to 2019; lists all macrocyclic diterpenoids that have been evaluated for their ability to inhibit viral replication. The structure–activity relationships and the probable involvement of protein kinase C in their mechanism of action are also detailed.

show abstract

Section: Protein Kinase C (Pkcs) As Targets Of Phorbol Esters For supporting

confidence: 77%

Section: Protein Kinase C (Pkcs) As Targets Of Phorbol Esters For mentioning

confidence: 99%

Macrocyclic Diterpenoids from Euphorbiaceae as A Source of Potent and Selective Inhibitors of Chikungunya Virus Replication

Rémy

Litaudon

2019

Molecules

View full text Add to dashboard Cite

show abstract

“…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%

Plant Secondary Metabolites as Anticancer Agents: Successes in Clinical Trials and Therapeutic Application

Seca

Pinto

2018

IJMS

494

303

View full text Add to dashboard Cite

Cancer is a multistage process resulting in an uncontrolled and abrupt division of cells and is one of the leading causes of mortality. The cases reported and the predictions for the near future are unthinkable. Food and Drug Administration data showed that 40% of the approved molecules are natural compounds or inspired by them, from which, 74% are used in anticancer therapy. In fact, natural products are viewed as more biologically friendly, that is less toxic to normal cells. In this review, the most recent and successful cases of secondary metabolites, including alkaloid, diterpene, triterpene and polyphenolic type compounds, with great anticancer potential are discussed. Focusing on the ones that are in clinical trial development or already used in anticancer therapy, therefore successful cases such as paclitaxel and homoharringtonine (in clinical use), curcumin and ingenol mebutate (in clinical trials) will be addressed. Each compound’s natural source, the most important steps in their discovery, their therapeutic targets, as well as the main structural modifications that can improve anticancer properties will be discussed in order to show the role of plants as a source of effective and safe anticancer drugs.

show abstract

“…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%

Marine Anticancer Agents: An Overview with a Particular Focus on Their Chemical Classes

et al. 2020

View full text Add to dashboard Cite

The marine environment is a rich source of biologically active molecules for the treatment of human diseases, especially cancer. The adaptation to unique environmental conditions led marine organisms to evolve different pathways than their terrestrial counterparts, thus producing unique chemicals with a broad diversity and complexity. So far, more than 36,000 compounds have been isolated from marine micro- and macro-organisms including but not limited to fungi, bacteria, microalgae, macroalgae, sponges, corals, mollusks and tunicates, with hundreds of new marine natural products (MNPs) being discovered every year. Marine-based pharmaceuticals have started to impact modern pharmacology and different anti-cancer drugs derived from marine compounds have been approved for clinical use, such as: cytarabine, vidarabine, nelarabine (prodrug of ara-G), fludarabine phosphate (pro-drug of ara-A), trabectedin, eribulin mesylate, brentuximab vedotin, polatuzumab vedotin, enfortumab vedotin, belantamab mafodotin, plitidepsin, and lurbinectedin. This review focuses on the bioactive molecules derived from the marine environment with anticancer activity, discussing their families, origin, structural features and therapeutic use.

show abstract

Natural Products as Lead Protein Kinase C Modulators for Cancer Therapy

Cited by 15 publications

References 154 publications

Macrocyclic Diterpenoids from Euphorbiaceae as A Source of Potent and Selective Inhibitors of Chikungunya Virus Replication

Macrocyclic Diterpenoids from Euphorbiaceae as A Source of Potent and Selective Inhibitors of Chikungunya Virus Replication

Plant Secondary Metabolites as Anticancer Agents: Successes in Clinical Trials and Therapeutic Application

Marine Anticancer Agents: An Overview with a Particular Focus on Their Chemical Classes

Contact Info

Product

Resources

About