New terpenoids from Maytenus apurimacensis as MDR reversal agents in the parasite Leishmania

Delgado-Méndez, Paulino; Hernandez, N. H.; Chávez, Haydee; Estévez‐Braun, Ana; Ravelo, Ángel G.; Cortés, Fernando; Castanys, Santiago; Gamarro, Francisco

doi:10.1016/j.bmc.2007.10.071

Cited by 26 publications

(19 citation statements)

References 25 publications

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“…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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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%

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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“…Some biologically active alkaloids, phenolic compounds, and terpenes have been isolated from some species of Maytenus (Celastraceae) [ 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. The triterpenes friedelin (3-oxofriedelane; 1 ), β -friedelinol (3 β -hydroxyfriedelane; 2 ), and 3,15-dioxo-21 α -hydroxyfriedelane ( 3 ) were isolated from the leaves of Maytenus robusta [ 15 , 16 , 17 ] ( Figure 1 ).…”

Section: Introductionmentioning

confidence: 99%

New Triterpenes from Maytenus robusta: Structural Elucidation Based on NMR Experimental Data and Theoretical Calculations

et al. 2012

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Leaves of Maytenus robusta (Celastraceae) were subjected to phytochemical investigation mainly directed at the isolation of pentacyclic triterpenes. The compounds friedelin (1), β-friedelinol (2), 3-oxo-21β-H-hop-22(29)-ene (7), 3,4-seco-friedelan-3,11β-olide (8), 3β-hydroxy-21β-H-hop-22(29)-ene (9), 3,4-seco-21β-H-hop-22(29)-en-3-oic acid (10), 3,4-seco-friedelan-3-oic acid (11), and sitosterol were identified in the hexane extract of M. robusta leaves. Compounds 8 and 9 are described herein for the first time. The structure and stereochemistry of both compounds were experimentally established by IR, HRLC-MS, and 1D (1H, 13C, and DEPT 135) and 2D (HSQC, HMBC and COSY) NMR data and supported by correlations with carbon chemical shifts calculated using the DFT method (BLYP/6-31G* level). Compounds 7 and 10 are also described for the first time, and their chemical structures were established by comparison with NMR data of similar structures described in the literature and correlations with BLYP/6-31G* calculated carbon chemical shifts. Compound 9, a mixture of 11 and sitosterol, and 3β,11β-dihydroxyfriedelane (4) were evaluated by the Ellman’s method and all these compounds showed acethylcholinesterase inhibitory properties.

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“…They are well recognized as chemotaxonomic markers or indicators of the family. Moreover, they are endowed with novel chemical diversity and complicated stereochemistry and possess a broad spectrum of biological activities such as insecticidal, MDR reversing activity, cytotoxic, antitumor-promoting, antitubercular, anti-HIV, immunosuppressive, and anti-inflammatory effects [9][10][11]. This data along with their structural characteristics make dihidro-βagarofuran sesquiterpenes to be considered as privileged structures.…”

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confidence: 99%

Dihydro-β-agarofuran Sesquiterpenoids fromPlenckia integerrima

Gutiérrez-Nicolás¹,

Oberti²,

Ariza-Espinar³

et al. 2011

Planta Med

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New terpenoids from Maytenus apurimacensis as MDR reversal agents in the parasite Leishmania

Cited by 26 publications

References 25 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

New Triterpenes from Maytenus robusta: Structural Elucidation Based on NMR Experimental Data and Theoretical Calculations

Dihydro-β-agarofuran Sesquiterpenoids fromPlenckia integerrima

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