azadiradione and nimbin

One new compound, 2H, 3H-cyclopent[b] furo [2',3':4,5] naphtho [2,4-d] heptlactone-[3,7] furan-6aceticacid, 3-(acetyloxy)-8-(3-furyl)-2a, 4a, 4b, 4c,5,5a, 6, 6a, 8, 9,9a, 10a,10b-13 hydrogen-2a,5a,6a,5-tetramethyl-3-[[(2E)-2-methyl-1-oxo-2-butenyl]oxy]-methyl ester, named azadirachta R (1), along with 10 known ones, Azadirachta A, AZ-B, AZ-D, AZ-H, AZ-I, nimbin, deacetylnimbin, salannin, deacetylsalannin and azadiradione were isolated from the crude extracts of neem (Azadirachta indica A. Juss) seeds, which were determined by UV, IR, HR-ESI-MS and NMR data analyses. According to the in vitro antibacterial activity experimental results, this compound showed good antibacterial activity to two bacteria, the minimum inhibitory concentration and the minimum bactericidal concentration of compound 1 to two kinds of bacteria are 50 and 25 mg/L, respectively, which were determined by resazurin colour-micro-dilution method. The experimental results provide a theoretical basis for the comprehensive utilisation of azadirachtin compounds in the future.

Topics: Anti-Bacterial Agents; Azadirachta; Drug Evaluation, Preclinical; Limonene; Limonins; Magnetic Resonance Spectroscopy; Microbial Sensitivity Tests; Molecular Structure; Plant Extracts; Seeds; Triterpenes

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