ABSTRACT
As a part of our investigation into new anti-HIV agents, we report herein the isolation, structure elucidation, and biological activity of six new (1-6) and 20 known (7-26) pentacyclic lupane-type triterpenoids from the stem of Cassine xylocarpa and root bark of Maytenus cuzcoina. Their stereostructures were elucidated on the basis of spectroscopic and spectrometric methods, including 1D and 2D NMR techniques. To gain a more complete understanding of the structural requirements for anti-HIV activity, derivatives 27-48 were prepared by chemical modification of the main secondary metabolites. Sixteen compounds from this series displayed inhibitory effects of human immunodeficiency virus type 1 replication with IC50 values in the micromolar range, highlighting compounds 12, 38, and 42 (IC50 4.08, 4.18, and 1.70 µM, respectively) as the most promising anti-HIV agents.
Subject(s)
Anti-HIV Agents/isolation & purification , Anti-HIV Agents/pharmacology , Celastraceae/chemistry , Maytenus/chemistry , Triterpenes/isolation & purification , Triterpenes/pharmacology , Anti-HIV Agents/chemistry , Antineoplastic Agents, Phytogenic/chemistry , HIV-1/drug effects , Humans , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Peru , Plant Bark/chemistry , Plant Stems/chemistry , Structure-Activity Relationship , Triterpenes/chemistryABSTRACT
In the present study, we report six cardiac glycosides (1-6) along with four known ones (7-10) isolated from the leaves and fruits of Elaeodendron orientale. Their stereostructures were elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR, and the absolute configuration of 1 was determined by X-ray diffraction analysis. The compounds were evaluated for growth inhibitory activity against a panel of human cancer cell lines, HeLa, A-549, MCF-7 and HL-60, and normal Vero cells. Four compounds from this series (5 and 7-9, IC50 values ranging from 0.01 to 0.07µM) exhibited cytotoxicity against three of the cancer cell lines assayed that was similar to or higher than the well-known therapies digoxin and digitoxigenin. Taking into account the narrow safety range of cardiac glycosides used in clinic, this series shows a selectivity index higher than 3 for three of the cancer cell lines assayed, increasing their interest for further study.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Cardenolides/isolation & purification , Cardenolides/pharmacology , Celastraceae/chemistry , Animals , Antineoplastic Agents, Phytogenic/chemistry , Cardenolides/chemistry , Chlorocebus aethiops , Digoxin/pharmacology , HL-60 Cells , HeLa Cells , Humans , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Plant Leaves/chemistry , Vero Cells , X-Ray DiffractionABSTRACT
In the present study we report the isolation of nine new olean-18-ene triterpenes (1-9), along with three known ones (10-12), from Cassine xylocarpa and Maytenus jelskii. Their stereostructures have been elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR techniques (COSY, ROESY, HSQC and HMBC), and spectrometric methods. The natural compounds and derivatives 13-15 have been tested for their potential as inhibitors of human immunodeficiency virus type 1 replication. Five compounds from this series displayed potent antiviral activity with IC(50)s in the micromolar range (1, 3, 4, 7 and 8) being 1 and 8 the most active compounds. The target of these compounds was different from antiretroviral drugs currently licensed as they act as inhibitors of enhancer-dependent transcription. The structure-activity relationships were established based on the regiosubstitution and oxidation degree of the triterpene scaffold, revealing that these aspects were able to modulate the selectivity and intensity of HIV inhibition.
