Cheiloclines A–I. First examples of octacyclic sesquiterpene-triterpene hetero-Diels–Alder adducts

Mesa-Siverio, Dulce; Chávez, Haydee; Estévez‐Braun, Ana; Ravelo, Ángel G.

doi:10.1016/j.tet.2004.10.074

Cited by 16 publications

(34 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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

Self Cite

View full text Add to dashboard Cite

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...

show abstract

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

Self Cite

View full text Add to dashboard Cite

show abstract

“…5 Hz, H-7), and an aromatic proton at δ 6.56 (H-1). With respect to the sesquiterpene unit derived from guaia-1(5),3(4), 11(3)-triene 18 ring were established by the NOEs observed in the ROESY spectrum ( Figure 4).…”

Section: Resultsmentioning

confidence: 94%

“…The 1 H NMR, 13 C NMR, and DEPT spectra revealed that 7 was a sesquiterpenetriterpene adduct. 18,43 Its 1 H NMR spectrum presented signals characteristic of a triterpenic unit related to the isotingenol series: 49 five methyl groups, one doublet methyl (δ 1.00, J ) 5.9 Hz), two vinylic protons at δ 6.67 (1H, dd, J ) 9.8, 2. 8 Hz, H-6) and 5.89 (1H, dd, J ) 9.8, 2.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Cytotoxic Triterpenoids from Maytenus retusa

et al. 2010

Self Cite

View full text Add to dashboard Cite

show abstract

“…The species of the Celastraceae biosynthesize dimeric [2] and trimeric [3] triterpenes, and octacyclic sesquiterpeneÀtriterpene adducts [4], possibly through hetero-DielsÀAlder reactions via the formation of a C(1)ÀC(4) dioxane system. Uragogin (triterpeneÀneolignan ester) and blepharodin (heptacyclic arylpropa-noidÀnortriterpene phenol) isolated from Crossopetalum uragoga and Maytenus magellanica, respectively, are examples of hetero-DielsÀAlder adducts endowed with dioxane bridges [5].…”

mentioning

confidence: 99%

Salicassin, an Unprecedented ChalconeDiterpene Adduct and a Quinone Methide Triterpenoid from Maytenus salicifolia

Magalhães

Silva

Duarte

et al. 2013

Helvetica Chimica Acta

View full text Add to dashboard Cite

In continuation of our work on Maytenus salicifolia, we report herein the isolation and structural elucidation of two new compounds, salicassin (1), a diterpene-chalcone adduct with an unprecedented Cframework, and (16b)-16-hydroxypristimerin (2), a quinone methide triterpenoid. Their structures were elucidated on the basis of spectroscopic analysis, including 1D-and 2D-NMR techniques (COSY, ROESY, HSQC, and HMBC). In addition, 22 known compounds were isolated and characterized by comparison of their spectra with reported data. Compound 2, structurally related to the well known cytotoxic quinone methide triterpenoids, exhibited an antiproliferative effect on HeLa, A-549, and HL-60 human cell lines, with IC 50 values of 2.2, 3.2, and 2.7 mm, respectively.Introduction. -The Maytenus genus, with more than 225 species, is widely distributed in the tropical and subtropical regions of the world, and represents the most diverse and richest genus of the Celastraceae family. In Brazil, 80 species of this genus have so far been documented as being present. Many traditional properties attributed to the Maytenus species have been experimentally verified, and these include antimitotic, antioxidant, and DNA polymerase b-lyase inhibitory activities [1].The species of the Celastraceae biosynthesize dimeric [2] and trimeric [3] triterpenes, and octacyclic sesquiterpeneÀtriterpene adducts [4], possibly through hetero-DielsÀAlder reactions via the formation of a C(1)ÀC(4) dioxane system. Uragogin (triterpeneÀneolignan ester) and blepharodin (heptacyclic arylpropa-noidÀnortriterpene phenol) isolated from Crossopetalum uragoga and Maytenus magellanica, respectively, are examples of hetero-DielsÀAlder adducts endowed with dioxane bridges [5]. Furthermore, the isolation of DielsÀAlder decacyclic C 20 -C 30 adducts [6] and diterpene dimers [7] [8] have also been reported for Celastraceae.Maytenus salicifolia Reissek is endemic in the state of Minas Gerais, southeast of Brazil, and is commonly known as cafezinho. Its leaves have been used in traditional

show abstract

Cheiloclines A–I. First examples of octacyclic sesquiterpene-triterpene hetero-Diels–Alder adducts

Cited by 16 publications

References 22 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

Cytotoxic Triterpenoids from Maytenus retusa

Salicassin, an Unprecedented ChalconeDiterpene Adduct and a Quinone Methide Triterpenoid from Maytenus salicifolia

Contact Info

Product

Resources

About