New clerodane diterpenoids from Laetia procera (Poepp.) Eichler (Flacourtiaceae), with antiplasmodial and antileishmanial activities

• Published in: Bioorganic & medicinal chemistry letters Vol. 15; no. 22; pp. 5065 - 5070
• Main Authors: Jullian, Valérie, Bonduelle, Colin, Valentin, Alexis, Acebey, Lucia, Duigou, Anne-Gaëlle, Prévost, Marie-Francoise, Sauvain, Michel
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15-11-2005; Elsevier
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antimalarials - chemistry; Antimalarials - pharmacology; Antineoplastic agents; Antiparasitic agents; Biological and medical sciences; Butanolide; Cell Line, Tumor; Clerodane diterpenoids; Diterpenes - chemistry; Diterpenes, Clerodane - chemistry; Flacourtiaceae; General aspects; Humans; Inhibitory Concentration 50; Laetia procera; Leishmania; Leishmania - drug effects; Magnetic Resonance Spectroscopy; Magnolia - chemistry; Medical sciences; Molecular Structure; Pharmacology. Drug treatments; Plasmodium falciparum; Plasmodium falciparum - drug effects; Structure-Activity Relationship; Flacourtiaceae; Butanolide; Plasmodium falciparum; Leishmania; Laetia procera; Clerodane diterpenoids; Antineoplastic agent; Antimalarial; Five membered ring; Bark; Cytotoxicity; NMR spectrometry; Selectivity; Oxygen heterocycle; Medicinal plant; Antiprotozoal agent; Dicotyledones; Angiospermae; Mammary gland; Secondary alcohol; Acylate; Tumor cell; Leishmania amazonensis; Kinetoplastida; Human; Protozoa; Terpenoid; Apicomplexa; Aliphatic compound; Pharmacognosy; Lactone; Tricyclic compound; In vitro; Biological activity; Cell line; Absolute configuration; Plant origin; Diterpene; Parasiticide; Isolation; Spermatophyta; Amastigote; Structural analysis; Promastigote
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2005.07.090

Together with two known compounds, Casearlucine A (
1) and Casearmembrol B (
2), four new clerodane diterpenoids and one new butanolide have been isolated from
Laetia procera (Flacourtiaceae). The six clerodane diterpenoids displayed activities against
Plasmodium falciparum,
Leishmania amazonensis, and human tumor cell line MCF7.
Extracts of
Laetia procera (Flacourtiaceae) displayed significant in vitro activity against
Plasmodium falciparum.
P. falciparum bioassay guided fractionation of a trunk bark extract of this plant led to the isolation of six clerodane diterpenoids (
1–
6) and a butanolide (
7). Five of these compounds are new and called Laetiaprocerine A–D (
3–
6) and Laetianolide A (
7). Their structures were established on the basis of 1D and 2D NMR experiments. Absolute configurations of
1 and
2 were determined by a modified Mosher’s method and the absolute configuration of
5 by chemical correlation. The clerodane diterpenoids displayed activities against
P. falciparum with an IC
50 down to 0.5
μM on FCb1 and F32 strains, and also cytotoxicity toward human tumor cell line MCF7. The most active compound showed a selectivity index of 6.8. Some of these compounds also displayed activities against
Leishmania amazonensis amastigote axenic stages and promastigote.