Anti-tumor-promotion by principles obtained from Angelica keiskei

Potent anti-tumor promoter activity has been found in the nonpolar extracts of the root of "Ashita-Ba", Angelica keiskei Koidz. (Umbelliferae), which is eaten as a vegetable in Japan. From this active fraction, two angular furanocoumarins, archangelicin (1) and 8(S),9(R)-9-angeloyloxy-8,9-dihydrooroselol (2), three linear furanocoumarins, psoralen (3), bergapten (4) and xanthotoxin (5), and three chalcones, 4-hydroxyderricin (6), xanthoangelol (7) and a novel chalcone named ashitaba-chalcone (8), were isolated. Among these compounds, two angular type furanocoumarins, 1 and 2, and three chalcones, 6-8, suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated 32Pi-incorporation into phospholipids of cultured cells, whereas coumarins 3-5 were less effective. In addition, chalcones 6 and 7 were proved to have anti-tumor-promoting activity in mouse skin carcinogenesis induced by 7,12-dimethylbenz[a]anthracene (DMBA) plus TPA. Since chalcones 6 and 7 showed calmodulin-interacting property, both chalcones may reveal anti-tumor-promoting activity via the modulation of calmodulin involved systems. These chalcones may be useful to develop the effective method for cancer prevention.     

穿心莲根的化学成分研究

为研究常用中药爵床科植物穿心莲(Andrographis paniculata)根的化学成分,运用各种色谱方法从安徽临泉产穿心莲根的80%乙醇提取物中分离并鉴定了28个化合物,其中20个黄酮:5,5'-二羟基-7,8,2'-三甲氧基黄酮(1)、5-羟基-7,8,2',6'-四甲氧基黄酮(2)、5,3'-dihydroxy-7,8,4',-trimethoxyflavone(3)、2'-羟基-5,7,8-三甲氧基黄酮(4)、5-羟基-7,8,2',3',4'-五甲氧基黄酮(6)、wightin(7)、5,2',6'-trihydroxy-7-methoxyflavone 2'-O-β-D-glucopyranoside(8)、5,7,8,2'-四甲氧基黄酮(10)、5-羟基-7,8-二甲氧基二氢黄酮(11)、5-羟基-7,8-二甲氧基黄酮(12)、5,2'-二羟基-7,8-二甲氧基黄酮(13)、5-羟基-7,8,2',5'-四甲氧基黄酮(14)、5-羟基-7,8,2',3'-四甲氧基黄酮(15)、5-羟基-7,8,2'-三甲氧基黄酮(16)、5,4'-二羟基-7,8,2',3'-四甲氧基黄酮(17)、二氢黄芩新...     

Synthesis and cytotoxicity of some rigid derivatives of methyl 2,5-Dihydroxycinnamate

Eight rigid compounds designed as esterase-stable analogues of methyl 2,5-dihydroxycinnamate (1) were synthesized. These derivatives include 2-(2',5'-dihydroxybenzylidene)cyclopentenone (3a), 2-(2',5'-dihydroxybenzylidene)cyclohexanone (3b), 2,6-bis(2',5'-dihydroxybenzylidene)cyclohexanone (4b), 2,6-bis(2',5'-dihydroxybenzylidene)cyclopentenone (4a), (E)-3-(2',5'-dihydroxybenzylidene)pyrrolidin-2-one (5), (E)-5-(2',5'-dihydroxybenzylidene)-1,2-isothiazolidine-1,1-dioxide (6), 4-(2',5'-dihydroxyphenyl)-5H-furan-2-one (7), and 3-(2',5'-dihydroxyphenyl)cyclopent-2-ene-1-one (8). Among the eight compounds, the furanone 7 and cyclopentenone 8 showed the most potent cytotoxicity with IC50 values of 0.39-0.98 microg/mL. Compound 8 was further brominated, phenylated and methylated at the alpha position to give three corresponding analogues, including 2-bromo-3-(2',5'-dihydroxyphenyl)cyclopent-2-ene-1-one (24), 3-(2',5'-dihydroxyphenyl)-2-phenylcyclopent-2-ene-1-one (27), and 3-(2',5'-dihydroxyphenyl)-2-methylcyclopent-2-ene-1-one (28). Among the three, the most enhanced activity was observed with the phenylated compound 27.     

The role of the hydrophobic group on ring A of chalcones in the inhibition of interleukin-5

Novel chalcones were found as potent inhibitors of interleukin-5 (11-5). 1-(6-Benzyloxy-2-hydroxyphenyl)-3-(4-hydroxyphenyl)propenone (2a, 78.8% inhibition at 50 microM, IC50 = 25.3 microM) was initially identified as a potent inhibitor of IL-5. This activity is comparable to that of budesonide or sophoricoside (1a). The benzyloxy group appears to be critical for the enhancement of the IL-5 inhibitory activity. To identify the role of this hydrophobic moiety, cyclohexyloxy (2d), cyclohexylmethoxy (2c), cyclohexylethoxy (2e), cyclohexylpropoxy (2f), 2-methylpropoxy (2g), 3-methylbutoxy (2h), 4-methylpentoxy (2i), and 2-ethylbutoxy (2j) analogs were prepared and tested for their effects on IL-5 bioactivity. Compounds 2c (IC50 = 12.6 microM), 2d (IC50 = 12.2 microM), and 2i (IC50 = 12.3 microM) exhibited the most potent activity. Considering the cLog P values of 2, the alkoxy group contributes to the cell permeability of 2 for the enhancement of activity, rather than playing a role in ligand motif binding to the receptor. The optimum alkoxy group in ring A of 2 should be one that provides the cLog P of 2 in the range of 4.22 to 4.67.     

Inhibition of cytochromes P450 by antifungal imidazole derivatives.

The interactions of a panel of antifungal agents with cytochromes P450 (P450s), as a means of predicting potential drug-drug interactions, have not yet been investigated. The objective of this study was to evaluate the specificity and selectivity of five antifungal agents using selective probe reactions for each of the eight major P450s. The index reactions used were phenacetin O-deethylation (for CYP1A2), coumarin 7-hydroxylation (CYP2A6), diclofenac 4'-hydroxylation (CYP2C9), omeprazole 5-hydroxylation (CYP2C19), dextromethorphan O-demethylation (CYP2D6), 7-ethoxy-4-trifluoromethylcoumarin deethylation (CYP2B6), chlorzoxazone 6-hydroxylation (CYP2E1), and omeprazole sulfonation (CYP3A4). Five antifungal agents that include an imidazole moiety (clotrimazole, miconazole, sulconazole, tioconazole, and ketoconazole) were examined in cDNA-expressing microsomes from human lymphoblast cells or human liver microsomes. All inhibitors studied demonstrated nonselective inhibition of P450s. Ketoconazole seemed to be the most selective for CYP3A4, although it also inhibited CYP2C9. High-affinity inhibition was seen for CYP1A2 (sulconazole and tioconazole K(i), 0.4 microM), CYP2B6 (miconazole K(i), 0.05 microM; sulconazole K(i), 0.04 microM), CYP2C19 (miconazole K(i), 0.05 microM; sulconazole K(i), 0.008 microM; tioconazole K(i), 0.04 microM), CYP2C9 (sulconazole K(i), 0.01 microM), CYP2D6 (miconazole K(i), 0.70 microM; sulconazole K(i), 0.40 microM), CYP2E1 (tioconazole K(i), 0.4 microM), and CYP3A4 (clotrimazole K(i), 0.02 microM; miconazole K(i), 0.03 microM; tioconazole K(i), 0.02 microM). Therefore, this class of compounds is likely to result in significant drug-drug interactions in vivo.     

Synthesis and anticonvulsant and neurotoxic properties of substituted N-phenyl derivatives of the phthalimide pharmacophore

A series of compounds including 4-amino (1), 3-amino (2), 4-nitro (3), 2-methyl-3-amino (4), 2-methyl-3-nitro (5), 2-methyl-4-amino (6), 2-methyl-4-nitro (7), 2-methyl-5-amino (8), 2-methyl-5-nitro (9), 2-methyl-6-amino (10), 2-methyl-6-nitro (11), 2,6-dimethyl (12), 2-methyl-3-carboxy (13), 2-methoxycarbonyl (14), 2-methyl-4-methoxy (15), 2,4-dimethoxy (16), 2-chloro-4-amino (17), and 2-chloro-4-nitro (18) N-phenyl substituents of phthalimide were evaluated along with N-[3-methyl-(2-pyridinyl)]phthalimide (19), N-(3-amino-2-methylphenyl)succinimide (20), and phenytoin for anticonvulsant and neurotoxic properties. Initial screening in the intraperitoneal (ip) maximal electroshock-induced seizure (MES) test and the subcutaneous pentylenetetrazol-induced seizure (scPtz) test in mice led to the selection of 1, 2, 4, 10, 12, 17, and 19 for oral MES evaluation in rats. The resultant ED(50) values for 4, 10, 17, and phenytoin were 8.0, 28.3, 5.7 and 29.8 mg/kg, respectively. In the batrachotoxin affinity assay, IC(50) values for 17 and phenytoin were 0.15 and 0.93 microM, respectively, and in the recently validated magnesium deficiency-dependent audiogenic seizure test, ED(50) values of 5.2 and 23 mg/kg were obtained for 17 and phenytoin, respectively. Electrophysiology studies on compound 17 point out its ability to (i) potentiate GABA-evoked current responses with a failure to directly activate the GABAA receptor and (ii) to affect, at 100 microM excitatory non NMDA, but not NMDA, receptors with a 25% block of kainate-evoked response. Electrophysiology measurements on voltage-gated sodium channels in N1E-115 neuroblastoma cells confirm voltage-dependent block of these channels by compound 17. In view of its interaction with multiple ion channels, one would predict that compound 17 might be active in a wide range of seizure models.     

The chemical constituents in the decoction of Urtica fissa rhizomes

Phytochemical investigation of the decoction of Urtica fissa rhizomes led to the isolation of 23 known compounds. Their structures were identified as medioresinol dimethyl ether (1), L-pyroglutamic acid methyl ester (2), nicotinic acid (3), L-pyroglutamic acid (4), erythritol (5), 6-methyl-2′-deoxy thymidine (6), 2-methyl-6-(2′,3′,4′-trihydroxybutyl)-pyrazine (7), 5-hydroxyl-2-hydroxymethyl pyridine (8) , adenine (9), uracil (10), thymine (11), adenosine (12), inosine (13), 2′-deoxyadenosine (14), 2′-deoxyguanosine (15), 2′-deoxyinosine (16), uridine (17), n-butyl-O-β-D-fructopyranoside (18), di-D-fructose (19), β-D-fructofuranosyl-α-D-galactopyranoside (20), bis (5-formyl-furfuryl) ether (21), chlorogenic acid (22), and 5-hydroxymethyl furaldehyde (23) by spectroscopic methods. In addition, a total of 20 compounds (1–20) were isolated from U. fissa for the first time. Meanwhile, compounds 1, 6, 7, 8, 19 and 20 were isolated from the Urticaceae plants for the first time.     

The Role of P2Y Receptors in the Control of Blood Pressure

Extracellular nucleotides have been implicated in a number of physiological functions. Nucleotides act on cell-surface receptors known as P2 receptors, of which several subtypes have been cloned. P2X receptors are ligand-gated ion channels, whereas P2Y receptors belong to the superfamily of G-protein-coupled receptors. The human P2Y-receptor family is composed of seven subtypes (P2Y(1), P2Y(2), P2Y(4), P2Y(6), P2Y(11), P2Y(12), P2Y(13)). The principal physiological agonists of the human P2Y receptors are ADP (P2Y(1), P2Y(12), P2Y(13)), UTP/ATP (P2Y(2)), UTP (P2Y(4)), UDP (P2Y(6)) and ATP (P2Y(11)). P2Y receptors are widely expressed in human tissues, and many subtypes are found in vascular smooth muscle cells and endothelial cells in blood vessels. The intracellular signaling of P2Y receptors is very complex. Activation of P2Y receptors in blood vessels induces vasodilation or vasoconstriction, prolifera- tion of vascular smooth muscle cells and Ca(2+)-sensitization. All mechanisms play an important role in blood pressure control and cardiovascular disease. (c) 2002 Prous Science. All rights reserved.     

Synthesis and antiviral activity of various 3'-azido analogues of pyrimidine deoxyribonucleosides against human immunodeficiency virus (HIV-1, HTLV-III/LAV)

Various 3'-azido analogues of pyrimidine deoxyribonucleosides have been synthesized and tested against human immunodeficiency virus (HIV-1, HTLV-III/LAV) in human peripheral blood mononuclear cells. Among these compounds, the 3'-azido analogues of thymidine (2), 3-(3-oxo-1-propenyl)thymidine (21), 2'-deoxyuridine (1), 2'-deoxy-5-bromouridine(5), 2'-deoxy-5-fluorocytidine (19), 2'-deoxy-5-iodouridine (6), 2'-deoxycytidine (18), 2'-deoxy-5-fluorouridine (4), 2'-deoxy-5-thiocyoanatouridine (16), 2'-deoxy-5-methylcytidine (20), 2'-deoxy-5-aminouridine (7), and 2'-deoxy-5-hydroxyuridine (10) were found to have significant antiviral activity, with EC50 values of 0.002, 0.01, 0.2, 1.0, 1.0, 1.1, 1.2, 4.8, 5.1, 5.1, 6.2, and 10 microM, respectively. The structure-activity relationships are discussed.     

Effects of nontoxic heat shock protein 90 inhibitor peptide derivatives on reversal of MDR of tumor cells

Novel heat shock protein 90 inhibitor peptide derivatives [D- Trp-Phe-D- Trp-Leu-AMB (1), p-HOPA-D- TrpPhe-D-Trp-Leu-psi(CH2NH)-Leu-NH2 (2), D-Trp-Phe-D-Trp-OH (3), Suc-D-Trp-Phe-D-Trp-Leu-AMB (4), D-Tyr-Phe-D-Trp-Leu-AMB (5), D-Arg-D-Trp-Phe-D-Trp-Leu-Leu-NH2 (6), Leu-psi(CH2NH)-Leu-NH2x2HCl (7), Phe-Trp-Phe-Trp-Leu-Leu-NH2 (8), Tyr-Trp-Phe-Trp-Leu-Leu-NH2 (9) and Tyr-D- Trp-Phe-D-Trp-Leu-Leu-NH2 (10)] were synthetized, and their ability to reverse multidrug resistance (MDR) was studied. Peptide derivatives 1, 4 and 5, with D-Trp or D-Tyr residues in the N-terminal position caused a marked inhibition of MDR in cancer cells. These MDR inhibitor compounds and epirubicin were demonstrated to have additive and synergistic antiproliferative effects in checkerboard experiments on human MDR1 gene-transfected mouse lymphoma cells in vitro. It is suggested that the MDR reversal effects of these anticancer peptide derivatives, together with their antiproliferative effects on lung cancer cells, may open up new horizons in cancer chemotherapy.     

当归化学成分的分离与鉴定

目的研究当归Angelica sinensis(Oliv.)Diels的化学成分,为其药理作用的研究奠定物质基础。方法采用硅胶柱色谱及制备薄层色谱等方法进行分离纯化,根据理化性质和波谱数据(1H-NMR、13C-NMR等)鉴定化合物的结构。结果分离得到13个化合物,分别鉴定为:正丁基苯酞(3-butylphthalide,1)、4羟基3丁基苯酞(4-hydroxy-3-butylphthalide,2)、2-methoxy-2-(4'-hydroxyphenyl)ethanol(3)、反式阿魏酸(ferulic acid,4)、厚朴酚(magnolol,5)、黄芩苷(baicalin,6)、2″O(2甲基丁酰基)异当药黄素[2″O(2-methylbutyryl)-isoswertisin,7]、harman(8)、1-ace-tyl-β-carboline(9)、酒渣碱(flazine,10)、菠菜甾醇(α-spinasterol,11)、异欧前胡素(isoimperatorin,12)、发卡二醇[3(R),8(S)-falcarindiol,13]。结论化合物3、7～9、11为首次从该属植物中分离得到,化合物5为首次从该植物中分离得到。     

巴戟天根皮中的醌类成分的分离与鉴定

目的研究巴戟天(Morinda officinalisHow.)化学成分。方法运用多种色谱学方法对巴戟天根皮体积分数70%乙醇提取物的化学成分进行分离,并根据光谱数据鉴定化合物的结构。结果从该植物中分离得到17个化合物,分别鉴定为rubiasin A(1)、rubiasin B(2)、2-羟基-1-甲氧基蒽醌(2-hydroxy-1-methoxy-anthraquinone,3)、3-羟基-1-甲氧基-2-甲基蒽醌(3-hydroxy-1-methoxy-2-methyl-anthraquinone,4)、1,3-二羟基-2-甲氧基蒽醌(1,3-dihydroxy-2-methoxy-anthraquinone,5)、2-甲基蒽醌(2-methyl-anthraquinone,6)、1,3-二羟基-2-甲基蒽醌(1,3-dihydroxy-2-methyl-anthraqui-none,7)、2-羟甲基蒽醌(2-hydroxymethyl-anthraquinone,8)、3-羟基-1,2-二甲氧基蒽醌(3-hydroxy-1,2-dimethoxy-anthraquinone,9)、1,8-二羟基-3-甲氧基-6-甲基蒽醌(1,8-dihydroxy-3-methoxy-6-methyl-anthraquinone,10)、苯乙醇-O-β-D-吡喃葡萄糖苷(2-phenylethyl-O-β-D-glucopyranoside,11)、2-丁醇-O-β-D-吡喃葡萄糖苷(sec-butyl-O-β-D-glucopyranoside,12)、3,4-二羟基苯乙醇(3,4-di-hydroxyphenylethanol,13)、3-(4-羟基-苯基)-1,2-丙二醇(3-(4-hydroxyphenyl)-1,2-propandiol,14)、阿魏酸(ferulic acid,15)、熊果酸(ursolic acid,16)、β-谷甾醇(β-sitosterol,17)。结论化合物1,2,11~14为首次从巴戟天属植物中分离得到。     

冬凌草地上部分的化学成分

目的从冬凌草(Rabdosia rubescensHemsl.)地上部分中提取分离活性成分。方法采用硅胶柱色谱等分离方法对冬凌草地上部分乙醇冷浸提取物进行分离,并通过NMR、ESI-MS和TLC等多种方法对分离得到的化学成分进行结构鉴定。结果分离得到15个化合物,分别鉴定为:α-香树脂醇(α-amyrin,1)、胡萝卜苷(daucosterol,2)、乌索酸(ursolic acid,3)、β-谷甾醇(β-sitosterol,4)、对映-7α,20-环氧-贝壳杉烷-16-烯-1α,6β,7β,14β,15β-五醇-1-O-葡萄吡喃糖苷(enmenol-glucoside,5)、lasiodonin(6)、葡萄糖(glucose,7)、2α,3α-二羟基-12-烯-28-乌索酸(2α,3α-dihydroxy-urs-12-en-28-oic acid,8)、冬凌草甲素(oridonin,9)、胡麻素(pedalitin,10)、肌醇(inositol,11)、冬凌草乙素(poni-cidin,12)、大叶晶B(dayecrystals B,13)、尿嘧啶(uracil,14)、邻苯二甲酸-二(2-乙基-2己基)酯[1,2-Benzenedicarboxylic acid bis(2-ethylhexyl)ester,15]。结论化合物14为首次从该属植物中分离得到,化合物8、13为首次从该植物中分离得到;邻苯二甲酸二-(2乙基-2己基)酯为实验材料中所引入的化合物。     

Mutagenicity screening of popular thai spices

Mutagenicity screening was carried out on 31 samples of popular Thai spices derived from 12 different families of plants, namely the Amaryllidaceae (2), Graminae (1), Labiatae (4), Lauraceae (1), Magnoliaceae (1), Myristicaceae (2), Myrtaceae (2), Piperaceae (3), Rutaceae (2), Solanaceae (2), Umbelliferae (2) and Zingiberaceae (9). Two variations of the rapid streak method of rec-assay in Bacillus subtilis strains H17 (rec+) and M45 (rec-) were used. Only Ceylon cinnamon (the bark of Cinnamomum zeylanicum Nees of the family Lauraceae) showed mutagenic activity. The crude form of this spice and its water-heated and water-macerated residues all produced the rec effect, while water-heated and water-macerated filtrates did not, even in concentrations equivalent to as much as 50 mg solids/test disc.     

番荔枝种子化学成分研究

目的研究药用植物番荔枝(Annona squamosa L)种子的抗肿瘤活性成分。方法利用各种色谱技术进行分离纯化, 根据化合物的理化性质和光谱数据鉴定化学结构。结果从乙醇提取物分离鉴定了11个番荔素: squamocenin (1), annotemoyin-2 (2), reticulatain-2 (3), squamocin-I (4), squamocin-B (5), squamocin (6), motrilin (7), squamostatin-D (8), squamostatin-E (9), cherimolin-1 (10)和cherimolin-2 (11)。结论Squamocenin (1)为新番荔素; annotemoyin-2 (2)和reticulatain-2 (3)是首次报道该植物含有的化合物。     

A New Minor Saponin from the Leaves of Panax ginseng

Seventeen compounds were isolated from the leaves of PANAX GINSENG C. A. Meyer. Among them, a new minor saponin was established as 3beta,6alpha,12beta-trihydroxy-dammar-20(22), 24-diene-6- O-alpha- L-rhamno-pyranosyl-(1-->2)-beta- D-glucopyranoside ( 2). Fourteen compounds were identified as 20( R)-protopanaxadiol ( 1), 20( R)-protopanaxatriol, ginsenoside-Rh (3), 20( R)-ginsenoside-Rh (2), 20( S)-ginsenoside-Rh (2), ginsenoside-Rh (1), -Rg (3), -Rg (2), -Rg (1), -Re, -Rd, -Rc, -Rb (2), -Rb (1); the others are still under investigation.     

Evaluation of the Dmt-Tic pharmacophore: conversion of a potent delta-opioid receptor antagonist into a potent delta agonist and ligands with mixed properties.

Analogues of the 2',6'-dimethyl-L-tyrosine (Dmt)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) pharmacophore were prepared to test the hypothesis that a "spacer" and a third aromatic center in opioid peptides are required to convert a delta-antagonist into ligands with delta-agonist or with mixed delta-antagonist/mu-agonist properties. Potent delta-agonists and bifunctional compounds with high delta- and mu-opioid receptor affinities were obtained by varying the spacer length [none, NH-CH(2), NH-CH(2)-CH(2), Gly-NH-CH(2)] and C-terminal aromatic nucleus [1H-benzimidazole-2-yl, phenyl (Ph) and benzyl groups]. C-terminal modification primarily affected mu-opioid receptor affinities, which increased maximally 1700-fold relative to the prototype delta-antagonist H-Dmt-Tic-NH(2) and differentially modified bioactivity. In the absence of a spacer (1), the analogue exhibited dual delta-agonism (pEC(50), 7.28) and delta-antagonism (pA(2), 7.90). H-Dmt-Tic-NH-CH(2)-1H-benzimidazole-2-yl (Bid) (2) became a highly potent delta-agonist (pEC(50), 9.90), slightly greater than deltorphin C (pEC(50), 9.56), with mu-agonism (pE(50), 7.57), while H-Dmt-Tic-Gly-NH-CH(2)-Bid (4) retained potent delta-antagonism (pA(2), 9.0) but with an order of magnitude less mu-agonism. Similarly, H-Dmt-Tic-Gly-NH-Ph (5) had nearly equivalent high delta-agonism (pEC(50), 8.52) and mu-agonism (pEC(50), 8.59), while H-Dmt-Tic-Gly-NH-CH(2)-Ph (6) whose spacer was longer by a single methylene group exhibited potent delta-antagonism (pA(2), 9.25) and very high mu-agonism (pEC(50), 8.57). These data confirm that the distance between the Dmt-Tic pharmacophore and a third aromatic nucleus is an important criterion in converting Dmt-Tic from a highly potent delta-antagonist into a potent delta-agonist or into ligands with mixed delta- and mu-opioid properties.     

The toxic torch of the modern Olympic Games

One of the most enduring symbols of the Olympics is the torch or flame, an icon of peace and sportsmanship that has its roots in Ancient Greece. According to the Creed of the Olympics: "The important thing in the Games is not winning, but taking part. The essential thing is not conquering. but fighting well." The modern Olympic Games (1896-2000) have been heavy laden with controversy, as athletes have abused performance enhancing drugs to thrust themselves into the limelight in search of gold. It was not until 1967 that the International Olympic Medical Commission began banning drugs. Full-scale drug testing was instituted in 1972.: Retrospective review of modern summer and winter Olympics Game sources (1896-2002) was done for documentation of drug abuse, drug-related overdoses, and positive drug screens. Data were collected for the type of drug documented. the athlete's name, their country of origin, and Olympic event. Seventy cases were identified. The most common class of agents were steroids (29), followed by stimulants (22), diuretics (7), beta-2 agonists (2), and beta blockers (1). Alcohol and marijuana, while not historically prohibited, have been outlawed by several individual sport federations. Toxicities of these 2 agents were most likely under-reported. Countries of origin of individual athletes included Bulgaria (7), USA (7), Sweden (4), Spain (4), Japan (2), Poland (2), Greece (2), Canada (2), Hungary (2), Russia (2), Austria (2), and Great Britain, Norway, Romania, Armenian, and Latvian, each with 1. The most common Olympic events in which drug abuse was documented were weightlifting (25), trackand field (12), skiing (5), wrestling (5), volleyball (3), modern pentathlon (3), cycling (2), swimming (2), gymnastics (1), and rowing (1). As athletic pressures and financial gains of the Olympic Games heighten, more toxicities are likely to occur despite attempts at restricting performance-enhancing drugs.     

Photolytic decomposition of indapamide.

Photolytic decomposition of indapamide (I) in nitrogen-flushed methanol yields 3-sulfamoyl-4-chlorobenzamide (II), 2-methylindoline (III), semicarbazide (IV), and 1-(N-formamido)-2-methylindoline (V); in oxygen-flushed methanol, II--V, 1-aminocarboxymethyl-2-methylindoline (VI), 3-sulfamoyl-4-chlorobenzoic acid (VII), methyl-3-sulfamoyl-4-chlorobenzoate (VIII), and 2-(N-acetamido)-benzoic acid (IX) are formed. A comparison is made with thermal decomposition of I.     

Four new benzofurans from seeds of Styrax perkinsiae

Four new benzofurans trans-5-(3-hydroxypropyl)-7-methoxy-2-[2,3-dihydro-3-hydroxymethyl-7-methoxy-2-(3-methoxy-4-hydroxyphenyl)-benzofuran-5-yl]benzofuran (1), (E)-5-(2-formylvinyl)-7-methoxy-2-(3,4-methylenedioxyphenyl)benzofuran (2), 5-(3-butanoyloxypropyl)-7-methoxy-2-(3,4-methylenedioxyphenyl)benzofuran (3), and 5-(3-hydroxypropyl)-7-hydroxy-2-(3,4-methylenedioxyphenyl) benzofuran (4) were isolated from the seeds of Styrax perkinsiae, together with egonol (5), demethoxyegonol (6), egonol acetate (7), demethoxyegonol acetate (8), egonol glucoside (9), egonol gentiobioside (10), egonol gentiotrioside (11), beta-sitosterol (12), and beta-daucosterol (13). Their structures were established by spectroscopic and chemical methods. Compounds 1 and 4 exhibited cytotoxic activity in vitro using two breast cancer cell lines MCF-7 and MDA-MB-231.