epoxyazadiradione and gedunin

Thirty-five limonoids, including 15 of the azadiradione type (1-15), five of the gedunin type (16-20), four of the azadirachtin type (21-24), nine of the nimbin type (25-33), and two degraded limonoids (34, 35), isolated from Azadirachta indica seed extracts, were evaluated for their cytotoxic activities against five human cancer cell lines. Seven compounds (3, 6, 7, 16, 18, 28, and 29) exhibited cytotoxic activity against one or more cell lines. Among these compounds, 7-deacetyl-7-benzoylepoxyazadiradione (7), 7-deacetyl-7-benzoylgeduin (18), and 28-deoxonimbolide (28) exhibited potent cytotoxic activity against HL60 leukemia cells with IC(50) values in the range 2.7-3.1 μM. Compounds 7, 18, and 28 induced early apoptosis in HL60 cells, observed by flow cytometry. Western blot analysis showed that compounds 7, 18, and 28 activated caspases-3, -8, and -9 in HL60 cells. This suggested that compounds 7, 18, and 28 induced apoptotic cell death in HL60 cells via both the mitochondrial- and the death receptor-mediated pathways. Futhermore, compound 7 was shown to possess high selective cytotoxicity for leukemia cells since it exhibited only weak cytotoxicity against a normal lymphocyte cell line (RPMI 1788).

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Azadirachta; Drug Screening Assays, Antitumor; HL-60 Cells; Humans; Limonins; Lymphocytes; Mitochondria; Molecular Structure; Receptors, Death Domain; Seeds

Eight known and two new triterpenoid derivatives, neemfruitins A (9) and B (10), have been isolated from the fruits of neem, Azadirachta indica, a traditional antimalarial plant used by Asian and African populations. In vitro antiplasmodial tests evidenced a significant activity of the known gedunin and azadirone and the new neemfruitin A and provided useful information about the structure-antimalarial activity relationships in the limonoid class.

Topics: Antimalarials; Azadirachta; Burkina Faso; Fruit; Limonins; Plants, Medicinal; Structure-Activity Relationship; Triterpenes

The major non-azadirachtin limonoids such as gedunin (1), epoxyazadiradione (3), nimbocinol (4), and nimolicinol (5) from Azadirachta indica A. Juss ('neem') and their derivatives were evaluated for their toxic action against fourth instar larvae of Aedes aegypti L. and Culex quinquefasciatus Say. Gedunin exhibited 100% toxic action against both the mosquito larvae at 50 and 10 ppm. Epoxyazadiradione and epoxynimolicinol also showed significant toxicities (> or =50%) against larvae of both mosquito species at 50 ppm. These neem limonoids can have benefits in mosquito-control programs.

Topics: Aedes; Animals; Azadirachta; Culex; Insecticides; Larva; Limonins; Plant Extracts; Seeds; Structure-Activity Relationship