Isolation, Structural Modification, and HIV Inhibition of Pentacyclic Lupane-Type Triterpenoids from Cassine xylocarpa and Maytenus cuzcoina.
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.
†Instituto Universitario de Bio-Orgánica "Antonio González", Universidad de La Laguna, Avenida Astrofísico Francisco Sánchez 2, 38206 La Laguna, Tenerife, Spain.
Oliver
O
Callies
‡Unidad de Inmunopatología, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Carretera Pozuelo Km.2, 28220-Majadahonda, Madrid, Spain.|§Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense de Madrid, Ramón y Cajal s/n, 28040, Madrid, Spain.
Luis M
LM
Bedoya
‡Unidad de Inmunopatología, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Carretera Pozuelo Km.2, 28220-Majadahonda, Madrid, Spain.
Manuela
M
Beltrán
‡Unidad de Inmunopatología, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Carretera Pozuelo Km.2, 28220-Majadahonda, Madrid, Spain.
Alejandro
A
Muñoz
‡Unidad de Inmunopatología, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Carretera Pozuelo Km.2, 28220-Majadahonda, Madrid, Spain.
Patricia Obregón
PO
Calderón
†Instituto Universitario de Bio-Orgánica "Antonio González", Universidad de La Laguna, Avenida Astrofísico Francisco Sánchez 2, 38206 La Laguna, Tenerife, Spain.
Alex A
AA
Osorio
†Instituto Universitario de Bio-Orgánica "Antonio González", Universidad de La Laguna, Avenida Astrofísico Francisco Sánchez 2, 38206 La Laguna, Tenerife, Spain.
Ignacio A
IA
Jiménez
‡Unidad de Inmunopatología, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Carretera Pozuelo Km.2, 28220-Majadahonda, Madrid, Spain.
José
J
Alcamí
†Instituto Universitario de Bio-Orgánica "Antonio González", Universidad de La Laguna, Avenida Astrofísico Francisco Sánchez 2, 38206 La Laguna, Tenerife, Spain.
Isabel L
IL
Bazzocchi
D019380:Anti-HIV Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry; D029753:Celastraceae / Q000737:chemistry*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D029755:Maytenus / Q000737:chemistry*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010568:Peru; D024301:Plant Bark / Q000737:chemistry; D018547:Plant Stems / Q000737:chemistry; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D053978:Pentacyclic Triterpenes
D019380:Anti-HIV Agents; D000972:Antineoplastic Agents, Phytogenic; D014315:Triterpenes; C480546:lupane; D053978:Pentacyclic Triterpenes