Natural polyprenylated benzophenones inhibiting cysteine and serine proteases

Martins, Felipe Terra; Assis, Diego M.; Santos, Marcelo H. dos; Camps, Ihosvany; Veloso, Márcia Paranho; Juliano, María A.; Alves, Lira C.; Doriguetto, Antônio C.

doi:10.1016/j.ejmech.2008.09.018

Cited by 55 publications

(35 citation statements)

References 33 publications

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“…Other mechanisms reported for protection of neuronal cells from oxidative damage are the following: i) direct free radical/reactive oxygen species scavenging capability and ii) inhibition of stress-induced caspases activation (46). In fact, garcinol, a prenylated benzophenone structurally related with GA, presents potent free radical scavenging activity (47) and enhances neuronal survival in neuron-astrocyte co-cultures with lipopolysaccharide (LPS) treatment, reducing the expression of LPS-induced inflammatory mediators (48).…”

Section: Discussionmentioning

confidence: 99%

A Strong Protective Action of Guttiferone-A, a Naturally Occurring Prenylated Benzophenone, Against Iron-Induced Neuronal Cell Damage

et al. 2011

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Abstract. Guttiferone-A (GA) is a natural occurring polyisoprenylated benzophenone with several reported pharmacological actions. We have assessed the protective action of GA on ironinduced neuronal cell damage by employing the PC12 cell line and primary culture of rat cortical neurons (PCRCN). A strong protection by GA, assessed by the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carbox-anilide (XTT)

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Section: Discussionmentioning

confidence: 99%

A Strong Protective Action of Guttiferone-A, a Naturally Occurring Prenylated Benzophenone, Against Iron-Induced Neuronal Cell Damage

et al. 2011

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“…Investigações farmacológicas de G. brasiliensis e seus compostos isolados de extratos mostraram atividades antianafiláticas (Neves et al, 2007), antimicrobiana (Almeida et al, 2008;Murata et al, 2008;Naldoni et al, 2009), antiespasmódica (Coelho et al, 2008), antiinflamatória e antioxidante (Martins et al, 2008;Santa-Cecília et al, 2011), antiproteolítica (Martins et al, 2009), antiproliferativa (Murata et al, 2010) e leishmanicida (Pereira et al, 2010), daí a relevância dos estudos realizados com esta espécie.…”

Section: Introductionunclassified

Estudo farmacobotânico das folhas de Garcinia brasiliensis Mart. (Clusiaceae)

Santa-Cecília

Abreu

Silva³

et al. 2013

Rev. bras. plantas med.

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RESUMO:A espécie Garcinia brasiliensis Mart. (Clusiaceae), nativa da região Amazônica e cultivada em todo o território brasileiro, vem sendo bastante estudada devido seu potencial farmacológico, porém são escassos estudos que tratam da caracterização farmacobotânica desta espécie. Considerando as propriedades terapêuticas para tornar-se um medicamento fitoterápico, o presente trabalho teve como objetivos estudar a anatomia e histoquímica da folha e do pecíolo e elaborar dados macroscópicos e microscópicos que forneçam características marcantes para sua identificação além de dar subsídios para a análise farmacognóstica no controle de qualidade da droga vegetal. O material vegetal foi fixado e submetido às técnicas usuais de microscopia de luz e a testes histoquímicos. As folhas de G. brasiliensis são opostas, simples, descolores, forma elíptica com nervação peninérvia. As células epidérmicas, em vista frontal, apresentam contorno sinuoso e estômatos paracíticos somente na face abaxial. O mesofilo é dorsiventral, a nervura central apresenta contorno biconvexo e feixe vascular em forma de semi-arco fechado envolto por bainha esclerenquimática. Inclusões inorgânicas de cristais na forma de drusas e orgânicas representadas por compostos fenólicos e grãos de amidos estão dispersos ao longo de toda lâmina foliar e pecíolo. Observa-se com frequência a presença de canais secretores preenchidos por um conteúdo lipídico dispersos pelo parênquima fundamental e próximos aos feixes vasculares. Estes dados fornecem subsídios para o controle de qualidade da matéria-prima utilizada para a produção de fitoterápicos.Palavras-chave: bacupari, Garcinia brasiliensis, Clusiaceae, morfodiagnose ABSTRACT: Pharmacobotanical studies of Garcinia brasiliensis Mart. (Clusiaceae) leaves. The Garcinia brasiliensis Mart. (Clusiaceae) species, native of the Amazon region and cultivated throughout the Brazilian territory, has been widely studied due to its pharmacological potential, but there are few studies dealing with the pharmacobotanic characterization of this species. Considering the therapeutic properties in order to become an herbal medicine, the present paper had the purpose of studying the anatomical and histochemical characterization of the leaf and petiole, as well as producing macroscopic and microscopic data that provide important characteristics for its identification, in addition to providing subsidies for the pharmacognostical analysis in order to offer elements for the quality assurance of the drug. The botanical material was prepared through the usual optical and histochemical microtechniques. The leaves of G. brasiliensis are simple, opposed, colorless, and they show an elliptical shape. As seen from the front, the epidermal cells have a sinuous contour, and paracytic stomata occur on the low surface. The leaves are hipostomatic and dorsiventral with heterogeneous mesophile. The mesophile is dorsiventral, the central midrib shows a biconvex contour and vascular system in a semi-closed arch shape surrounded by a sclerenchymatic...

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“…Substrate hydrolyses were monitored in a spectrofluorometer F2500 Hitachi, and the enzymatic molar concentrations were estimated by titration according to kinetic parameters (Martins et al, 2009). …”

Section: Enzymesmentioning

confidence: 99%

“…Trypsin (E.C. 3.4.21.4) has specificity for peptides containing Arg and Lys residues, and its catalytic triad is composed of the amino acids serine, histidine and aspartate, which is similar to other serine proteases (Martins et al, 2009;Beynon, 1989). Each amino acid of the triad has a specific role in the peptide bond cleavage of the substrates.…”

Section: Introductionmentioning

confidence: 99%

“…These enzymes can be further joined according to the reactant groups that are present in the catalytic site, as serine (EC 3.4.21), cysteine (EC 3.4.22), aspartic acid (EC 3.4.23), metalo (EC 3.4.24) and threonine (EC 3.4.25) proteases. Papain (EC 3.4.22.2), a plant cysteine protease isolated from Carica papaya latex, preferentially cleaves peptide chains on either Arg and Lys residues or hydrophobic Phe residues (Brocklehurst, 1987;Martins et al, 2009). Trypsin (E.C.…”

Section: Introductionmentioning

confidence: 99%

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Morelloflavone and its semisynthetic derivatives as potential novel inhibitors of cysteine and serine proteases

Gontijo¹,

Januário²,

Júdice³

et al. 2015

J. Med. Plants Res.

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This article reports the three biflavonoids isolated from the fruit pericarp of Garcinia brasiliensis Mart. (Clusiaceae): Morelloflavone-4```-glycoside (compound 1), (±)-Fukugiside (compound 2), and Morelloflavone (compound 3). Structural modifications by acylation and alkylation reactions were performed on the natural biflavonoid (±) morelloflavone to obtain three semisynthetic compounds: Morelloflavone-7,4`,7``,3```,4```-penta-O-acetyl (compound 4), Morelloflavone-7,4`,7``,3```,4```-penta-Omethyl (compound 5), and Morelloflavone-7,4`,7``,3```,4```-penta-O-butanoyl (compound 6). The inhibitory effects of these naturally isolated biflavonoid-type compounds and three semisynthetic derivatives on the activity of the cysteine proteases papain and cruzain, and on the serine protease trypsin were investigated. The potential inhibitory IC 50 of natural bioflavonoids compounds 1, 2, and 3 were 11.0 ± 3.0, 23.0 ± 4.0, and 10.5 ± 0.3 µM, respectively, for papain; 0.86 ± 0.12, 106 ± 7, and 3.8 ± 0.1, 50 ± 2, 119.5 ± 5, and 9.6 ± 1.0 µM, respectively, for cruzain. On the other hand, the semisynthetic biflavonoids compounds 4, 5, and 6 were more efficient in the inhibition of enzyme activity with IC 50 values 0.60 ± 0.02 µM (papain) for biflavonoids compound 4, 1.64 ± 0.11 µM (trypsin) for biflavonoids compound 5, and 8.1 ± 0.6 µM (cruzain) for biflavonoids compound 6. Compound 4 is more active owing to the carbonyl group in the structure; perhaps, this modification could favor a higher nucleophilic attack by serine and cysteine proteases. However, the semisynthetic compound 5 (IC 50 = 15.4 ± 0.7 µM for papain), which has no carbonyl group in structure, was less active in the inhibition. Interestingly, structure-activity relationships (SARs) were confirmed by flexible docking simulations. Likewise, the potential usefulness of natural compound 1 as an antioxidant compound was strengthened by our results concerning the antiproteolytic activity.

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Natural polyprenylated benzophenones inhibiting cysteine and serine proteases

Cited by 55 publications

References 33 publications

A Strong Protective Action of Guttiferone-A, a Naturally Occurring Prenylated Benzophenone, Against Iron-Induced Neuronal Cell Damage

A Strong Protective Action of Guttiferone-A, a Naturally Occurring Prenylated Benzophenone, Against Iron-Induced Neuronal Cell Damage

Estudo farmacobotânico das folhas de Garcinia brasiliensis Mart. (Clusiaceae)

Morelloflavone and its semisynthetic derivatives as potential novel inhibitors of cysteine and serine proteases

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