Novel DNA‐Damaging Tropolone Derivatives from <i>Goupia glabra</i>

Mesa-Siverio, Dulce; Estévez‐Braun, Ana; Ravelo, Ángel G.; Murguía, José Ramón; Rodríguez-Afonso, Abigail

doi:10.1002/ejoc.200300284

Cited by 32 publications

(33 citation statements)

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“…13 C NMR spectra were recorded at 75 and 100 MHz using Bruker AMX300 and AMX400 instruments. Carbon spectra assignments were supported by DEPT-135 spectra, 13 C-1 H (HMQC), and 13 C-1 H (HMBC) correlations where necessary. Chemical shifts are quoted in ppm and are referenced to the appropriate residual solvent peak.…”

Section: Chemistrymentioning

confidence: 99%

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The Lupane-type Triterpene 30-Oxo-calenduladiol Is a CCR5 Antagonist with Anti-HIV-1 and Anti-chemotactic Activities

Barroso-González

Jaber-Vazdekis

García-Expósito

et al. 2009

Journal of Biological Chemistry

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The existence of drug-resistant human immunodeficiency virus (HIV) viruses in patients receiving antiretroviral treatment urgently requires the characterization and development of new antiretroviral drugs designed to inhibit resistant viruses and to complement the existing antiretroviral strategies against AIDS. We assayed several natural or semi-synthetic lupane-type pentacyclic triterpenes in their ability to inhibit HIV-1 infection in permissive cells. We observed that the 30-oxo-calenduladiol triterpene, compound 1, specifically impaired R5-tropic HIV-1 envelope-mediated viral infection and cell fusion in permissive cells, without affecting X4-tropic virus. This lupane derivative competed for the binding of a specific anti-CCR5 monoclonal antibody or the natural CCL5 chemokine to the CCR5 viral coreceptor with high affinity. 30-Oxo-calenduladiol seems not to interact with the CD4 antigen, the main HIV receptor, or the CXCR4 viral coreceptor. Our results suggest that compound 1 is a specific CCR5 antagonist, because it binds to the CCR5 receptor without triggering cell signaling or receptor internalization, and inhibits RANTES (regulated on activation normal T cell expressed and secreted)-mediated CCR5 internalization, intracellular calcium mobilization, and cell chemotaxis. Furthermore, compound 1 appeared not to interact with ␤-chemokine receptors CCR1, CCR2b, CCR3, or CCR4. Thereby, the 30-oxocalenduladiol-associated anti-HIV-1 activity against R5-tropic virus appears to rely on the selective occupancy of the CCR5 receptor to inhibit CCR5-mediated HIV-1 infection. Therefore, it is plausible that the chemical structure of 30-oxo-calenduladiol or other related dihydroxylated lupane-type triterpenes could represent a good model to develop more potent anti-HIV-1 molecules to inhibit viral infection by interfering with early fusion and entry steps in the HIV life cycle. The human immunodeficiency virus (HIV)7 pandemic is a medical challenge and represents the public health crisis of our time (1-5). Antiretroviral treatment achieves long-lasting viral suppression and, subsequently, reduces the morbidity and mortality of HIV-infected individuals. However, current drugs do not eradicate HIV infection and lifelong treatment might be needed (2).Emerging drug-resistant HIV viruses, in patients receiving high active antiretroviral treatment, urgently needs the development of new antiretroviral molecules designed to inhibit resistant viruses, because many patients treated during the past decades harbor viral strains with reduced susceptibilities to many if not all available drugs (2, 6). In this matter, pentacyclic triterpenes represent a varied class of natural products presenting antitumor and antiviral activities (7-9). A well studied pentacyclic lupane-type triterpene is the betulinic acid (3␤-hydroxy-lup-20(29)-en-28-oic acid), widely distributed throughout the plant kingdom, which presents anti-inflammatory, anti-malarial, and anti-HIV-1 effects in vitro (7, 9, 10). Although its mechanism of action has not been f...

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Section: Chemistrymentioning

confidence: 99%

“…Compounds 1-3 and 5 were semi-synthesized as described below, whereas natural compounds 4 and 6 were isolated from Maytenus apurimacensis, using a previously described method (12)(13)(14)(15)(16). The degree of purity of the tested compounds was estimated higher than 99% by NMR spectroscopy.…”

Section: Chemistrymentioning

confidence: 99%

The Lupane-type Triterpene 30-Oxo-calenduladiol Is a CCR5 Antagonist with Anti-HIV-1 and Anti-chemotactic Activities

Barroso-González

Jaber-Vazdekis

García-Expósito

et al. 2009

Journal of Biological Chemistry

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“…Com grande potencial para investigações na área médica, há indicações de que a cupiúba também possa fornecer matéria-prima para as indústrias farmacêuticas, principalmente as que trabalham com substâncias químicas que inibam efeitos cancerígenos (Mesa-Siverio et al, 2003), agregando, assim maior valor de mercado à espécie.…”

Section: Introductionunclassified

Comportamento da castanha-do-brasil (Bertholletia excelsa) e da cupiúba (Goupia glabra) em sistema agrosilvicultural na região da Confiança, Cantá - Roraima

Ferreira

Tonini

2009

Acta Amaz.

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RESUMOO presente trabalho objetivou estudar o desempenho das espécies castanha-do-brasil (Bertholetia excelsa) e cupiúba (Goupia glabra) e o ajuste de uma função de crescimento e uma equação para estimar o diâmetro de copa em um modelo de sistema agroflorestal -SAF implantado em 1995 no Campo Experimental Confiança, Cantá, Estado de Roraima. Foram medidas 71 árvores de castanheira e 50 de cupiúbas totalizando 121 árvores, sendo tomados o CAP (circunferência a 1,30 m do solo), altura total, altura de inserção da copa, diâmetro da copa e dados qualitativos como sobrevivência, qualidade do fuste, bifurcações e aspectos fitossanitários como doenças ou pragas. Das 71 árvores de castanheira avaliadas 20 (27,8%) produziram frutos. A cupiúba apresentou alta porcentagem de indivíduos com bifurcação (cerca de 87,5%). A análise estatística indicou a função de Backman como a de melhor ajuste para as espécies observadas e com base nas equações construídas para estimar o diâmetro da copa em função do DAP pode-se fazer inferências sobre o espaço vital necessário para atingir uma determinada dimensão. Ambas as espécies apresentaram potencial silvicultural para recuperação de áreas alteradas em sistemas agroflorestais ou plantios homogêneos. PALAVRAS-CHAVE:Bertholletia excelsa, goupia glabra, sistemas agroflorestais, Roraima.Behavior of castanha-do-brasil (Bertholletia excelsa) and cupiúba (Goupia glabra) in an agrosilvicultural system in Confiança region, Cantá -Roraima State (1) ABSTRACT The aim of this present work was to study the behavior of castanha-do-brasil (Bertholletia excelsa) and cupiúba (Goupia glabra) and also set a growing function and an equation for estimating the crown diameter in an agroforestry system model, installed in Confiança Experimental Station, Cantá, Roraima, Brazil, in 1995. We measured quantitative data, such as diameter basal height, total height, crown insertion height, crown diameter and qualitative data like survival, bole quality and phytosanitary aspects such as disease or pests. We analyzed the silvicultural behavior and estimated equation at the crown diameter in function of DBH, and adjusted a growing function for the cupiuba and castanha-do-brasil. Of the 71 castanha-do-brasil trees analyzed 20 (27,8%) producing fruits. The cupiúba showed high individual percentage of bifurcation (around 87,5%). The statistical analyses indicated the Backman function as the best adjusted for the observed species; and based on the equations for estimating crown diameter in function of DBH, we could make inferences about the necessary vital space for reaching determinated dimension. Both species have silvicultural potential for restored areas in agroforestry systems or homogeneous plantations.

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“…[1] Since 1 and 2 behave as genotoxins that are stronger than the antineoplastic agent doxorubicin, they are candidates for anticancer drugs. [1] Goupiolone A (1) is a benzotropolone derivative [1,2] and presumed to be produced from catechol (3) and ethyl gallate (4) by oxidative coupling via a benzobicyclo[3.2.1]octane-type intermediate (Scheme 1). Other benzotropolone derivatives from natural sources, such as purpurogallin glycosides, [3] theaflavins, [4] fomentariol, [5] aurantricholone, [6] and crocipodin, [7] are also produced by the coupling between catechol and pyrogallol derivatives.…”

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Structural Revision and Biomimetic Synthesis of Goupiolone B

et al. 2017

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Goupiolones A and B are unique phenolic compounds with significant DNA-damaging activity. In this study, the structure of goupiolone B was revised on the basis of DFT calculations of the 13 C NMR chemical shifts and biosynthetic considerations. The dibenzobicyclo[3.2.2]nonane skeleton of the revised structure suggested that goupiolone B was produced by oxidative coupling between catechol and goupiolone A, which was strongly supported by this biomimetic synthesis. Furthermore, the racemization of goupiolone B was observed during the examination for the chiral separation of its racemic mixture. A plausible racemization mechanism involving α-ketol rearrangement was also proposed.

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Novel DNA‐Damaging Tropolone Derivatives from Goupia glabra

Cited by 32 publications

References 29 publications

The Lupane-type Triterpene 30-Oxo-calenduladiol Is a CCR5 Antagonist with Anti-HIV-1 and Anti-chemotactic Activities

The Lupane-type Triterpene 30-Oxo-calenduladiol Is a CCR5 Antagonist with Anti-HIV-1 and Anti-chemotactic Activities

Comportamento da castanha-do-brasil (Bertholletia excelsa) e da cupiúba (Goupia glabra) em sistema agrosilvicultural na região da Confiança, Cantá - Roraima

Structural Revision and Biomimetic Synthesis of Goupiolone B

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