Kazuo Koike

Three new and other limonoids from the hexane extract of Melia azedarach fruits and their cytotoxic activities.

A defatted fraction obtained from the hexane extract of the fruits of Melia azedarach L. (chinaberry tree; Meliaceae) exhibited cytotoxic activities against leukemia (HL60), lung (A549), stomach (AZ521), and breast (SK‐BR‐3) cancer cell lines with IC50 values in the range of 2.9–21.9u2005μg/ml. Three new limonoids, 3‐deacetyl‐4′‐demethylsalannin (5), 3‐deacetyl‐28‐oxosalannin (14), and 1‐detigloylohchinolal (17), along with 16 known limonoids, 1–4, 6–13, 15, 16, 18, and 19, and one known triterpenoid, 20, were isolated from the fraction. The structures of new compounds were elucidated on the basis of extensive spectroscopic analyses and comparison with literature. These compounds were evaluated for their cytotoxic activities against the four cancer cell lines mentioned above. 3‐Deacetyl‐4′‐demethyl‐28‐oxosalannin (16), which exhibited potent cytotoxicity against AZ521 (IC50 3.2u2005μM) cells, induced typical apoptotic cell death in AZ521 cells upon evaluation of the apoptosis‐inducing activity by flow cytometry. This work provided, furthermore, valuable information on the structural features of limonoids of the fruits and/or seeds of Melia azedarach and related Meliaceae plants, M. toosendan and Azadirachta indica.

4α-Methyl-5α,14β-ergosta-8,24(241)-dien-3β-ol (“triticusterol”): the first naturally occurring 14β(H)-steroid

The structure of triticusterol isolated from the germ oil of wheat (Triticum aestivum L.; Gramineae) was established to be 4α-methyl-5α,14β-ergosta-8,24(241)-dien-3β-ol on the basis of spectroscopic data. This is the first example of a naturally occurring compound with a 14β(H)-steroid skeleton.

QSAR Studies of Picrodendrins and Related Terpenoids — Structural Differences Between Antagonist Binding Sites on GABA Receptors of Insects and Mammals

γ -Aminobutyric acid (GABA), an inhibitory neurotransmitter, binds to the GABAA (ionotropic) receptor, to regulate the central nervous system of vertebrates. Insects have similar ionotropic receptors with different pharmacological properties, and, as a result, their GABA receptors represent promising targets for insecticides. Recently, 3D-QSAR analyses for insecticidal activity (against houseflies) and competitive activity against the specific [35S]tert-butylbicyclophosphorothionate (TBPS) binding (to rat brain membranes) of some picrotoxinin-type GABA antagonists, including γ -BHC, endosulfan, bicyclophophates, dioxatricyclododecenes (DTD) and related compounds, were carried out1 using comparative molecular field analysis (CoMFA). The CoMFA results showed that similarities and dissimilarities in sterically and electrostatically favourable and forbidden regions on the molecule were reflected in the insecticidal and rat-receptor binding activities.