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The conformational properties of a series of pyridoxal amino acid Schiff's bases have been calculated. The calculations were performed using the program CAMSEQ which employs a set of empirical potential energy functions. The cndo/2 charge distributions are also given in this preliminary report. The locations of the local energy minima are consistent with Dunathan's hypothesis that the course of enzymatic reaction is related to the conformation of the pyridoxal phosphate Schiff's base. Calculated results are also in agreement with experiment.

Cytotoxicity-guided fractionation of an organic solvent extract of the plant Crossosoma bigelovii led to the discovery of a new strophanthidin glycoside (1) and two new 2-methylchromone glycosides (2 and 3). Also isolated were the known chromones eugenin and noreugenin, the indole alkaloid ajmalicine, the dibenzylbutane lignan secoisolariciresinol, the dibenzylbutyrolactone lignan matairesinol, and the furanone 5-tetradec-5-enyldihydrofuran-2-one. Further investigation into the biological properties of strophanthidin glycosides revealed a connection between inhibition of HIF-1 activation and the glycosylation of the genin. This work is the first published study of the bioactive phytochemicals of the family Crossosomataceae.

D-501036 [2,5-bis(5-hydroxymethyl-2-selenienyl)-3-hydroxymethyl-N-methylpyrrol], a novel selenophene derivative, is a highly potent cytotoxic agent with broad spectrum antitumor activity. The present study was undertaken to explore the mechanism(s) through which D-501036 exerts its action mode on the cancer cell death. D-501036 was found to suppress the growth of KB and HepG(2) cells in an irreversible manner. The results of annexin-V assays and PARP cleavage studies were consistent with the D-501036-induced apoptosis. Findings provided a strong support for the induction of mitochondria-mediated apoptosis by this drug. The examination of two canonical pathways of initiation caspases, those for caspases -8 and -9, revealed that caspase-9 protein and the activities of caspases -9 and -3 were increased in a dose- and time-dependent manner. The concentrations of Fas/Fas-L and procaspase-8 and the activity of caspase-8 were not altered. Furthermore, the mitochondrial membrane potential permeability and the release of cytochrome c to the cytosol were both increased by D-501036. The concentrations of the pro-apoptotic protein Bax and translocation of Bax from the cytosol to the mitochondria were increased in response to D-501036, whereas the concentrations of the anti-apoptotic protein Bcl-2 were decreased. Two DNA damage-related pro-apoptotic proteins, Puma and Noxa, were upregulated in a dose- and time-dependent manner. These pro-apoptotic and anti-apoptotic proteins are downstream effectors of p53. Accordingly, the phosphorylated and total forms of p53 were induced and p53 was translocated from the cytosol to the mitochondria in response to D-501036 treatment. Collectively, we conclude that D-501036 induces cellular apoptosis through the p53-associated mitochondrial pathway.

D-501036 [2,5-bis(5-hydroxymethyl-2-selenienyl)-3-hydroxymethyl-N-methylpyrrole] is herein identified as a novel antineoplastic agent with a broad spectrum of antitumoral activity against several human cancer cells and an IC50 value in the nanomolar range. The IC50 values for D-501036 in the renal proximal tubule, normal bronchial epithelial, and fibroblast cells were >10 μmol/L. D-501036 exhibited no cross-resistance with vincristine- and paclitaxel-resistant cell lines, whereas a low level of resistance toward the etoposide-resistant KB variant was observed. Cell cycle analysis established that D-501036 treatment resulted in a dose-dependent accumulation in S phase with concomitant loss of both the G0-G1 and G2-M phase in both Hep 3B and A-498 cells. Pulsed-field gel electrophoresis showed D-501036–induced, concentration-dependent DNA breaks in both Hep 3B and A-498 cells. These breaks did not involve interference with either topoisomerase-I and topoisomerase-II function or DNA binding. Rapid reactive oxygen species production and formation of Se-DNA adducts were evident following exposure of cells to D-501036, indicating that D-501036–mediated DNA breaks were attributable to the induction of reactive oxygen species and DNA adduct formation. Moreover, D-501036–induced DNA damage activated ataxia telangiectasia–mutated nuclear protein kinase, leading to hyperphosphorylation of Chk1, Chk2, and p53, decreased expression of CDC25A, and up-regulation of p21WAF1 in both p53-proficient and p53-deficient cells. Collectively, the results indicate that D-501036–induced cell death was associated with DNA damage–mediated induction of ataxia telangiectasia–mutated activation, and p53-dependent and -independent apoptosis pathways. Notably, D-501036 shows potent activity against the growth of xenograft tumors of human renal carcinoma A-498 cells. Thus, D-501036 is a promising anticancer compound that has strong potential for the management of human cancers. [Mol Cancer Ther 2007;6(1):193–202]

Purpose. To identify hydrotropic agents that can increase aqueous paclitaxel (PTX) solubility and to study the chemical structures necessary for hydrotropic properties so that polymeric hydrotropic agents can be synthesized.

For the development of new anticancer agents, 2,2':6',2"-, 2,2':6',3"- and 2,2':6',4"-terpyridine derivatives were designed and evaluated for their topoisomerase I inhibitory activity and antitumor cytotoxicity. Structure-activity relationship studies indicated that 2,2':6',2"-terpyridine derivatives were highly cytotoxic toward several human tumor cell lines, whereas 2,2':6',3"- and 2,2':6',4"-terpyridine derivatives were potent topoisomerase I inhibitors.

A series of alpha-terthiophene derivatives were prepared and their protein kinase C inhibitory activity were evaluated. The aldehyde derivatives were most potent inhibitors (IC501 microM). alpha-Terthiophene monoaldehyde was inactive in the inhibitions of protein kinase A, mitogen activated protein kinase and protein tyrosine kinase.

5′-Deoxy-6-thioguanosine, 2′,5′-dideoxy-6-thioguanosine, 5′-deoxy-6-mercaptopurine riboside and 2′,5′-dideoxy-6-mercaptopurine riboside were synthesized enzymatically from thiopurine bases and corresponding ribosyl donors using nucleoside phosphorylase. This is the first report of trans-5′-deoxyribosylation to thiopurine bases by nucleoside phosphorylase. 5′-Deoxy-6-thioguanosine selectively blocked the growth of v-ras-transformed human bronchial epithelial cells. In addition, the in vitro antitumor cytotoxicity data for 5′-deoxy- and 2′,5′-dideoxy-6-thiopurine nucleosides were comparable to those for the corresponding thiopurine bases.

We have previously shown that emodin suppresses tyrosine kinase activity of HER-2/neu-encoded p185neu receptor tyrosine kinase. In this study, we examine the relationship between the chemical structure and the activity of emodin and nine derivatives, and identified that one methyl, one hydroxy, and one carbonyl functional groups are critical for the biological activities of emodin. We also found that one of the derivatives 10-(4-acetamidobenzylidene)-9-anthrone (DK-V-47) is more effective than emodin in repressing the tyrosine phosphorylation of p185neu and in inhibiting the proliferation and transformation of HER-2/neu-overexpressing human breast cancer cells. Using mutation-activated HER-2/neu transformed 3T3 cells, we also investigated whether emodin and DK-V-47 can inhibit malignant transformation induced solely by the HER-2/neu oncogene. We found that DK-V-47 is more potent than emodin in suppressing transformation phenotypes of activated HER-2/neu transformed 3T3 cells including anchorage-dependent and -independent growth, metastasis-associated properties. These results clearly indicate that the inhibition of p185neu tyrosine kinase by both emodin and DK-V-47 is capable of suppressing the HER-2/neu associated transformed phenotypes including the ability to induce metastatic potential. Our results also support the chemotherapeutic implications of the use of either emodin or DK-V-47 to target HER-2/neu-overexpressing cancer cells.

A novel heterocyclic compound, psorothamnone A was isolated from Psorothamnus junceus and its structure was determined by spectroscopic methods.

Emodin (3-methyl-1,6,8-trihydroxyanthraquinone) was shown to be an interesting protein-tyrosine kinase, p56lck inhibitor initially isolated from Polygonum cuspidatum. A series of modified emodin analogs were synthesized and examined for inhibitory activity against protein-tyrosine kinase and protein kinase C, and for cytotoxicity against human tumor cell lines. None of the emodin derivatives is a strong protein kinase C inhibitor. All emodin analogs are not highly cytotoxic agent. Current results coincide with the previous data on selective inhibition of the growth of ras-transformed human lung and Her-2/neu-overexpressed human breast tumor cells, suggesting that protein-tyrosine kinase inhibition may play an important role in the growth inhibitory activity of emodin analogs.

One new taxoid, 7-deacetyldecinnamoyltaxuspine B (1), and five known taxoids were isolated using silica gel chromatography from the crude methanolic extract of Taxus X media “Dark Green Spreader”. Their structures, were determined based on extensive spectroscopic analysis. The known compounds were determined to be taxuspine F (2), taxinine A (3), 2-deacetoxy-13-deacetyldecinnamoyltaxinine J (4), 2-deacetoxydecinnamoyltaxinine J (5), and 1-acetyl-10-deacetylbaccatin III (6).

Three new cytotoxic norditerpenoid dilactones, purdilactones A {1}, B {2} and C {3}, were isolated from the alcoholic extracts of Podocarpus purdieanus Hook. These compounds exhibited in vitro cytotoxicity in 9PS mouse lymphocytic leukemia and in human tumor cell lines A-549 (lung carcinoma), MCF-7 (breast adenocarcinoma) and HT-29 (colon adenocarcinoma).

A new prenylated flavanone 1 [laxiflorin (2S)-5,7,3′,4′-tetrahydroxy-6-(β-hydroxyethyl)-8-(γ,γ-dimethylallyl)flavanone] and four known flavanones (6,8-diprenyleriodictyol, hiravanone, senegalensein and lupinifolin) were isolated from the leaves and twigs of Derris laxiflora. Laxiflorin with a β-hydroxyethyl group at C-6 exhibited significant inhibitory activity against protein-tyrosine kinase.

Two new taxanes-1-hydroxy-5-decinnamoyl taxinine J (1) and 1-hydroxy taxinine A (2), and seven known taxanes were isolated using silica gel chromatography from the needles of Taxus x. media Hicksii. Their structures were primarily determined by detailed spectroscopic analysis. The known compounds have been characterized as taxol (3), cephalomannine (4), baccatin III (5), taxinine (6), taxinine M (7), 1-hydroxy-5-deacetyl baccatin I (8) and taxyuntin (9).

Meliavolin ( 1 ), a new triterpene with an apotirucallane skeleton, and meliavolkin ( 2 ), a new tetranortriterpene, together with melianin A, a known compound, have been isolated from the root bark of Melia volkensii (Meliaceae) by using activity-directed fractionation with brine shrimp. The structures have been elucidated by spectral data. The relative and absolute stereochemistry of meliavolin ( 1 ) was determined by analysis of Mosher ester derivatives, 1e and 1f , and by X-ray crystallographic analysis of meliavolin diacetate, 1c. 1 and melianin A showed marginal cytotoxicities to certain human tumor cell lines, but 2 was significantly more cytotoxic, showing equivalent potency to adriamycin against the human breast tumor cell line (MCF-7).

Two new bioactive apotirucallane triterpenes, meliavolkensins A ( 1 ) and B ( 2 ), were isolated from the root bark of Melia volkensii (Meliaceae). These two compounds have a new type of substituted tetrahydropyran ring side chain, and their structures have been elucidated by spectroscopic analyses. 1 and 2 also show cytotoxic selectivities to a hyman colon tumor cell line (H-29).

Chemical investigation of the cytotoxic fraction of Koelreuteria henryi resulted in the isolation of three cyclolignans. A new cyclolignan, named koelreuterin-1 was elucidated as furo[3',4':6,7]naphtho[2,3-d]-1,3-dioxol-6(8H)-one,5-(7-methoxy-1, 3- benzodioxol-5-yl)[1]. Two known cyclolignans were characterized as austrobailignan-1 [2] and austrobailignan-2 [3]. The structure elucidation of 1 was based on extensive 1H- and 13C-nmr spectral analyses. Further chemical conversion of 2 to 3 and oxidative transformation of 2 to 1 unambiguously confirmed the structure of 1. The cytotoxicity and tubulin polymerization inhibitory activity of 1-3 are discussed.

The biosynthesis of naphthomycin A (1) in Streptomyces collinus was studied in feeding experiments with single and multiple 13C-labeled precursors followed by 13C NMR analysis of the labeling and 13C–13C coupling patterns in the product. The results indicate that 1 is assembled via the polyketide pathway from 3-amino-5-hydroxybenzoic acid (2) as the starter unit (mC7N unit) plus seven propionate and six acetate chain extension units. 2 is synthesized via the shikimate pathway by a process that attaches the nitrogen to the carbon derived from C1 of erythrose 4-phosphate, consistent with a new branch of the shikimate pathway recently discovered to operate in the biosynthesis of the mC7N unit of rifamycin B.

Two novel xanthones, psorofebrin and 5′-hydroxyisopsorofebrin, containing a fused tetrahydrofurobenzofuran ring system, two new members of the dihydr

Bioassay-directed fractionation of a medicinal plant, Polygonum cuspidatum (Polygonaceae), has led to the discovery of a hydroxystilbene, resveratrol [1], as an inhibitor of a protein-tyrosine kinase (p56lck) partially purified from bovine thymus. Both trans and cis isomers of resveratrol possess comparable protein-tyrosine kinase inhibitory activity. Comparison of the IC50 values of resveratrol for protein-tyrosine kinase inhibitory activity with those of piceid (resveratrol-O3-beta-glucoside) [2] and resveratrol-O4'-beta-glucoside [3] shows the requirement of free hydroxyl groups on both phenyl rings for the protein-tyrosine kinase inhibition. Protein kinase C inhibitory analysis suggests the requirements of two free hydroxyl groups on one phenyl ring only.

Emodin (3-methyl-1,6,8-trihydroxyanthraquinone), a naturally occurring protein-tyrosine kinase inhibitor, selectively blocked the growth of v-ras-transformed human bronchial epithelial cells. Half-maximal inhibition of cell growth occurred at a concentration of 4 micrograms/ml. In contrast, emodin at a concentration of 100 micrograms/ml had little effect on the growth of normal human bronchial epithelial cells. Cell cycle analyses indicated that treatment with emodin arrested the v-ras-transformed cells in the G2/M phase of their cell cycle. Immunoblotting experiments using anti-phosphotyrosine antibodies indicated that ras-transformed cells, as compared to their normal counterparts, exhibited elevated levels of phosphotyrosine-containing proteins. Treatment with emodin resulted in a decrease in intracellular protein-tyrosine phosphorylation. These results suggest that compounds that inhibit the ras-dependent elevation in the level of tyrosine phosphorylated proteins may prove to be useful chemotherapeutic agents and may exhibit selective cytotoxicity against cancer cells with an activated ras oncogene.

Ohioensins A (1), B (2), C (3), D (4), and E (6), containing the novel polycyclic skeleton of (7bβ,-12bα,14cα)-7b,12b,13,14c-tetrahydro-14H-benzo[c]naphtho[2,1,8-mna]xanthen-14-one,have been isolated from the moss Polytrichum ohioense (Polytrichaceae) following bioassay-directed fractionation. The structures and relative stereochemistry of ohioensins were established on the basis of spectral analysis (UV, IR, MS, 2D NMR, and CD), chemical correlation, and X-ray diffraction

Bioconversion of taxol/cephalomannine by Streptomyces sp. MA 7065 resulted in hydroxylation on the 10-acetyl methyl group in 60% yield and on the benzene ring at the para position of the phenylisoserine side chain in 10% yield. This culture could also hydroxylate the allylic methyl group of the phenylisoserine side chain of cephalomannine quantitatively. All three metabolites were cytotoxic toward human lung, breast and colon tumor cell lines.

Three new styryllactones, goniobutenolides A (1) and B (3) and goniofupyrone (5), have been isolated from the bark of Goniothalamusgiganteus (Annonaceae). The structures were elucidated by ir, ms, 1H nmr, 13C nmr, 1H-1H COSY, nOe difference, and NOESY spectra. These compounds are marginally cytotoxic to human tumor cells in culture.

Two novel eight-membered-ring lactones, gonioheptolides A (1 and B (3), have been isolated from the bark of Goniothalamus giganteus. The structures were elucidated by IR, MS, 1H and 13C NMR, COSY, HMQC, HMBC, and NOESY spectra. 1 and 3 showed marginal cytotoxicities to certain human solid tumor cells in culture. A biogenetic pathway of the 14 styryllactones found in G. giganteus is proposed.

Two new bioactive apotirucallane triterpenes, meliavolkensins A ( 1 ) and B ( 2 ), were isolated from the root bark of Melia volkensii (Meliaceae). These two compounds have a new type of substituted tetrahydropyran ring side chain, and their structures have been elucidated by spectroscopic analyses. 1 and 2 also show cytotoxic selectivities to a hyman colon tumor cell line (H-29).

5′-Deoxy-6-thioguanosine, 2′,5′-dideoxy-6-thioguanosine, 5′-deoxy-6-mercaptopurine riboside and 2′,5′-dideoxy-6-mercaptopurine riboside were synthesized enzymatically from thiopurine bases and corresponding ribosyl donors using nucleoside phosphorylase. This is the first report of trans-5′-deoxyribosylation to thiopurine bases by nucleoside phosphorylase. 5′-Deoxy-6-thioguanosine selectively blocked the growth of v-ras-transformed human bronchial epithelial cells. In addition, the in vitro antitumor cytotoxicity data for 5′-deoxy- and 2′,5′-dideoxy-6-thiopurine nucleosides were comparable to those for the corresponding thiopurine bases.

A series of β-substituted polythiophene derivatives was synthesized through palladium-catalyzed coupling reaction. Their structure-protein kinase C (PKC) inhibitory activity relationship was studied. The carboxaldehyde and hydroxymethyl derivatives of α-terthiophene were potent PKC inhibitors (IC 50 = 10 −7 M).

A bioactivity-directed fractionation of the ethanolic extracts of Robinia pseudoacacia L. (Fabaceae) afforded robinlin (1), a novel homo-monoterpene. The structure of 1 was elucidated by spectral analyses of the parent compound as well as its derivatives; 1 showed strong bioactivity in the brine shrimp lethality test (BST).

Three new linear polyketides, 10,13-trans-13,14-erythro-densicomacin (1), 10,13-trans-13,14-threo-densicomacin (2), and 8-hydroxyannonacin (3), and a known polyketide goniothalamicin were isolated from the stem bark of the Peruvian plant Annona densicoma Mart (Annonaceae). Their structures were elucidated on the basis of UV, IR, 1 H and 13 C NMR, and mass spectrometry data of the natural compounds and their derivatives. These polyketides are cytotoxic against human tumor cells in culture

Quantitation of 3-methylthymidine and O4-methylthymidine generated in the reaction of calf thymus DNA with methyl methanesulfonate (MeMS) and 1-methyl-1nitrosourea (MeNU) by mass spectrometry is reported. Quantitative precision of 7% or better is achieved on samples of 10−12 −10−13 mole in the HPLC and a final stage of separation before quantification by tandem mass spectrometry using desorption chemical ionization. Synthetic CD3-labeled nucleosides were used as internal standards for mass spectral quantification. A unique mass spectrometric scanning procedure, which allowed simultaneous MS—MS product ion analysis of both the analyte and the internal standard, was utilized to enchance precision and accuracy in these low level determinations. MeNU (a potent carcinogen) resulted in 18&%; 3-methylation and 0.17% O4-methylation of deoxythymidine whereas MeMS (a weak carcinogen) produced only 6.8% 3-methylation and 0.005% of deoxythymidine. These results demonstrate that the sensitivity and accuracy of this method should be adequate for the detection and quantification of methyl-nucleosides at the sub-picomole level at which mutation is induced in cell cultures.

Three new styryllactones, goniobutenolides A (1) and B (3) and goniofupyrone (5), have been isolated from the bark of Goniothalamusgiganteus (Annonaceae). The structures were elucidated by ir, ms, 1H nmr, 13C nmr, 1H-1H COSY, nOe difference, and NOESY spectra. These compounds are marginally cytotoxic to human tumor cells in culture.

Activity-directed fractionation of the stem bark of Annona squamosa, monitoring with brine shrimp lethality, led to the isolation of the highly bioactive acetogenins bullatacin [1] and bullatacinone [2], thus demonstrating a new abundant plant source for these potent compounds. A new keto-monotetrahydrofuran acetogenin with a ketolactone terminus, as first seen in bullatacinone [2], was also isolated, characterized by spectral analyses, and named squamone [3]. The cytotoxicities of 3 were increased significantly by reduction of the two keto groups to hydroxyls, and the tetrahydrosquamone [7] and bullatacinone [2] both showed selective cytotoxicities to MCF-7 human breast carcinoma. Liriodenine and (-)-kaur-16-en-19-oic acid were also isolated.

By guiding fractionation with brine shrimp lethality, three novel compounds, with cytotoxic activities against human tumor cell lines, have been isolated from the bark of Melodorum fruticosum Lour.(Annonaccae). These compounds have benzoyl moieties in common with a c7 dienone or lactone terminal which appears to arise from a heptose or the equivalents. They were named melodienone, isomelodienone, and acetylmelodorinol.

Recent advances in the chemistry of novel bioactive natural products are reported. This research is directed to the exploration of plants with confirmed activity in bioassays designed to detect potential cancer chemotherapeutic and chemopreventive agents. Structural work and chemical studies are reported for several cytotoxic agents from the plants Annona densicoma, Annona reticulata, Claopodium crispifolium, Polytrichum obioense, and Psorospermum febrifugum. Studies are also reported based on development of a mammalian cell culture benzo[a]pyrene metabolism assay for the detection of potential anticarcinogenic agents from natural products. In this study a number of isoflavonoids and flavonoids with antimutagenic activity have been discovered.

Mark E. Stearns (Chairperson),1* Joy L. Ware (Rapporteur),2 David B. Agus,3 Ching-Jer Chang,4 Isaiah J. Fidler,5 Rose S. Fife,6 Robin Goode,7 Eric Holmes,8 Michael S. Kinch,9 Donna M. Peehl,10 Thomas G. Pretlow II,11 and George N. Thalmann12 1Department of Pathology, Medical College of Pennsylvania and Hahnemann University, Philadelphia, Pennsylvania 2Department of Pathology, Virginia Commonwealth University, Richmond, Virginia 3Memorial Sloan-Kettering Cancer Center, New York, New York 4Department of Medicinal Chemistry, Purdue University, West Lafayette, Indiana 5Department of Cell Biology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 6Indiana University School of Medicine, Indianapolis, Indiana 7Lilly Research Laboratories, Indianapolis, Indiana 8Pacific Northwest Cancer Foundation, Seattle, Washington 9Department of Basic Medical Sciences, Purdue University, West Lafayette, Indiana 10Department of Urology, Stanford University, Stanford, California 11Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 12Universitat Bern, Bern, Switzerland

An alkaloidal extract of the vines of Stephania japonica showed multidrug-resistance-reversing activity as demonstrated by the bicinchoninic acid assay. Two known bisbenzylisoquinoline alkaloids, isotrilobine (1) and trilobine (2), were isolated by bioassay-directed fractionation and separation. Isotrilobine (1) was shown to be as active as verapamil (3) in reversing doxorubicin resistance in human breast cancer cells.

Brine shrimp lethality-directed fractionation of the 95% EtOH extract of the powdered dried bark of Persea americana Mill. var. americana (Lauraceae) led to the isolation of one new C 20 alkyl-alkene acetonyl methyl ester designated persealide (1). Persealide showed moderate cytotoxicity against three solid tumor cell lines: human lung carcinoma (A-549), human breast carcinoma (MCF-7) and human colon adenocarcinoma (HT-29).

To identify hydrotropic agents that can increase aqueous paclitaxel (PTX) solubility and to study the chemical structures necessary for hydrotropic properties so that polymeric hydrotropic agents can be synthesized.More than 60 candidate hydrotropic agents (or hydrotropes) were tested for their ability to increase the aqueous PTX solubility. A number of nicotinamide analogues were synthesized based on the observation that nicotinamide showed a favorable hydrotropic property. The identified hydrotropes for PTX were used to examine the structure-activity relationship.N,N-Diethylnicotinamide (NNDENA) was found to be the most effective hydrotropic agent for PTX. The aqueous PTX solubility was 39 mg/ml and 512 mg/ml at NNDENA concentrations of 3.5 M and 5.95 M, respectively. These values are 5-6 orders of magnitude greater than the intrinsic solubility of 0.30 +/- 0.02 microg/ml. N-Picolylnicotinamide, N-allylnicotinamide, and sodium salicylate were also excellent hydrotropes for PTX. Solubility data showed that an effective hydrotropic agent should be highly water soluble while maintaining a hydrophobic segment.The present study identified several hydrotropic agents effective for increasing aqueous solubility of PTX and analyzed the structural requirements for this hydrotropic property. This information can be used to find other hydrotropic compounds and to synthesize polymeric hydrotropes that are effective for PTX and other poorly water-soluble drugs.

A bioactivity-directed fractionation of the ethanolic extracts of Robinia pseudoacacia L. (Fabaceae) afforded robinlin (1), a novel homo-monoterpene. The structure of 1 was elucidated by spectral analyses of the parent compound as well as its derivatives; 1 showed strong bioactivity in the brine shrimp lethality test (BST).

The cytotoxicity of the dominant lignans and sesquiterpenoids from Taiwania (Taiwania cryptomerioides Hayata) was investigated. Three human tumor cells including A-549 lung carcinoma. MCF-7 breast adenocarcinoma and HT-29 colon adenocarcinoma were selected to illustrate the structure-cytotoxicity relationships of Taiwania's dominant compounds. Taiwanin A, taiwanin E and dimethylmatairesinol exhibited significant cytotoxicity against three human tumor cells. Among them, taiwanin A possesses the strongest cytotoxic activity. In addition, the morphology-based evaluation, flow cytometric analysis, and DNA fragmentation assays demonstrated that the tumor cell death induced by taiwanin A was due to apoptosis.