Synthesis and Antitumor Activity of Diterpenylhydroquinone Derivatives of Natural Ent-Labdanes

Espinoza, Luis; Maturana, Evelyn Baeza; Marín, Karen Catalán; Olivares, Mauricio Osorio; Altamirano, Héctor Carrasco; Fritis, Mauricio Cuellar; García, Joan Villena

doi:10.3390/molecules15096502

Cited by 9 publications

(8 citation statements)

References 17 publications

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“…Prenylated compounds with one or more prenyl moieties are common natural products that have been isolated predominantly from marine organisms and plants [ 1 , 2 , 3 , 4 ]. These compounds have attracted much attention because they often possess antimicrobial, antioxidant, anti-inflammatory, antiviral and anticancer activities [ 5 , 6 , 7 , 8 ]. Various attempts to establish structure–activity relationships (SARs) relating to these biological activities with structural features of metabolites and their derivatives have been made [ 1 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and in Vitro Antifungal Activity against Botrytis cinerea of Geranylated Phenols and Their Phenyl Acetate Derivatives

Chávez

Soto

Taborga

et al. 2015

IJMS

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The inhibitory effects on the mycelial growth of plant pathogen Botritys cinerea have been evaluated for a series of geranylphenols substituted with one, two and three methoxy groups in the aromatic ring. The results show that the antifungal activity depends on the structure of the geranylphenols, increasing from 40% to 90% by increasing the number of methoxy groups. On the other hand, the acetylation of the –OH group induces a change of activity that depends on the number of methoxy groups. The biological activity of digeranyl derivatives is lower than that exhibited by the respective monogeranyl compound. All tested geranylphenols have been synthesized by direct coupling of geraniol and the respective phenol. The effect of solvent on yields and product distribution is discussed. For monomethoxyphenols the reaction gives better yields when acetonitrile is used as a solvent and AgNO3 is used as a secondary catalyst. However, for di- and trimethoxyphenols the reaction proceeds only in dioxane.

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Section: Introductionmentioning

confidence: 99%

Synthesis and in Vitro Antifungal Activity against Botrytis cinerea of Geranylated Phenols and Their Phenyl Acetate Derivatives

Chávez

Soto

Taborga

et al. 2015

IJMS

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“…As a part of our ongoing interest in developing new and efficient antitumour agents, we recently reported the synthesis of two new hemisynthetic diterpenylhydroquinones from natural ent -labdanes by coupling between an arene nucleus and an allylic alcohol, which showed important activity in the inhibition of the growth of cancerigenous cells [ 9 , 10 ]. This kind of molecules are structural analogs of terpenylquinones and terpenylhydroquinones which are characteristic marine metabolites frequently isolated from alga and/or sponge [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and DPPH Radical Scavenging Activity of Prenylated Phenol Derivatives

et al. 2012

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The synthesis of twenty six prenylated phenols derivatives is reported. These compounds were obtained under mild conditions via Electrophilic Aromatic Substitution (EAS) coupling reactions between phenol derivatives containing electron-donor subtituents and 3-methyl-2-buten-1-ol using BF3·OEt2. Dialkylations were also produced with this method. The formation of a chroman ring by intramolecular cyclization between a sp2 carbon from the prenyl group with the hydroxyl substituent in the ortho position occurred with some phenols. All the synthesized compounds were evaluated as antioxidants according to a DPPH radical scavenging activity assay. IC50 values of five synthesized compounds indicated they were as good antioxidants as Trolox™.

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“…Terpenylquinones comprise a class of marine natural products considered attractive scaffolds for drug design due to their ubiquity in nature and their versatile bioactivities [1]. These compounds are characterized as having a bicyclic sesquiterpene skeleton coupled to a quinone 4 moiety [2]. Among them, ilimaquinone (IQ) ( Fig.…”

Section: Introductionmentioning

confidence: 99%

Mechanism of irreversible inhibition of Mycobacterium tuberculosis shikimate kinase by ilimaquinone

Simithy

Fuanta

Hobrath

et al. 2018

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

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Ilimaquinone (IQ), a marine sponge metabolite, has been considered as a potential therapeutic agent for various diseases due to its broad range of biological activities. We show that IQ irreversibly inactivates Mycobacterium tuberculosis shikimate kinase (MtSK) through covalent modification of the protein. Inactivation occurred with an apparent second-order rate constant of about 60 M s. Following reaction with IQ, LC-MS analyses of intact MtSK revealed covalent modification of MtSK by IQ, with the concomitant loss of a methoxy group, suggesting a Michael-addition mechanism. Evaluation of tryptic fragments of IQ-derivatized MtSK by MS/MS demonstrated that Ser and Thr residues were most frequently modified with lesser involvement of Lys and Tyr. In or near the MtSK active site, three residues of the P-loop (K15, S16, and T17) as well as S77, T111, and S44 showed evidence of IQ-dependent derivatization. Accordingly, inclusion of ATP in IQ reactions with MtSK partially protected the enzyme from inactivation and limited IQ-based derivatization of K15 and S16. Additionally, molecular docking models for MtSK-IQ were generated for IQ-derivatized S77 and T111. In the latter, ATP was observed to sterically clash with the IQ moiety. Out of three other enzymes evaluated, lactate dehydrogenase was derivatized and inactivated by IQ, but pyruvate kinase and catalase-peroxidase (KatG) were unaffected. Together, these data suggest that IQ is promiscuous (though not entirely indiscriminant) in its reactivity. As such, the potential of IQ as a lead in the development of antitubercular agents directed against MtSK or other targets is questionable.

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Synthesis and Antitumor Activity of Diterpenylhydroquinone Derivatives of Natural Ent-Labdanes

Cited by 9 publications

References 17 publications

Synthesis and in Vitro Antifungal Activity against Botrytis cinerea of Geranylated Phenols and Their Phenyl Acetate Derivatives

Synthesis and in Vitro Antifungal Activity against Botrytis cinerea of Geranylated Phenols and Their Phenyl Acetate Derivatives

Synthesis and DPPH Radical Scavenging Activity of Prenylated Phenol Derivatives

Mechanism of irreversible inhibition of Mycobacterium tuberculosis shikimate kinase by ilimaquinone

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