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A quantitative structure–activity relationship (QSAR) study was carried out on 112 anticancer compounds to develop a robust model for the prediction of anti-leukemia activity (pGI 50 ) against MOLT-4 and P388 leukemia cell lines. The Genetic algorithm (GA) and multiple linear regression analysis (MLRA) were used to select the descriptors and to generate the correlation models that relate the structural features to the biological activities. The final equations consist of 15 and 10 molecular descriptors calculated using the paDEL molecular descriptor software. The GA-MLRA analysis showed that the Conventional bond order ID number of order 1 (piPC1), number of atomic composition (nAtomic), and Largest absolute eigenvalue of Burden modified matrix – n 7/weighted by relative mass (SpMax7_Bhm) play a significant role in predicting the anticancer activities of these compounds. The best QSAR model for MOLT-4 was obtained with R 2 value of 0.902, Q 2 LOO = 0.881 and R 2 pred = 0.635, while for P388 cell line R 2 = 0.904, Q 2 LOO = 0.856 and R 2 pred = 0.670. The Y-scrambling/randomization validation also confirms the statistical significance of the models. These models are expected to be useful for predicting the inhibitory activity (pGI50) against MOLT-4 and P388 leukemia cell lines.

An unprecedented bis-indole 1, a novel indole alkaloid 2, and some known indole-related compounds 3–5 have been isolated from the sponge Plakortis sp. collected from Zampa in Okinawa. Their structures were elucidated by spectroscopic analysis. These metabolites showed cytotoxic activity against P388 leukemia and B16 melanoma cells.

Seven new limonoids, dysomollides A-G (1-7), and two new cycloapotirucallane-type triterpenoids, dysomollins A and B (8 and 9), together with three known compounds, dysoxylumin A (10) and toonapubesins A (11) and B (12), were isolated from the twigs of Dysoxylum mollissimum var. glaberrimum. The structures of 1-9 were elucidated on the basis of spectroscopic methods. Compound 10 showed inhibitory activity against A549 cells with an IC50 value of 2.1 μM, and compound 11 exhibited activity against P388 cells with an IC50 value of 6.7 μM.

The soil-derived bacterium, Streptomyces sp. CJ-5, was cocultured with the mycolic acid-containing bacterium Tsukamurella pulmonis TP-B0596. The combined culture method significantly enhanced the production of the secondary metabolites in Streptomyces sp. CJ-5, leading to the isolation of three novel butanolide chojalactones A-C (1-3), with unusual γ-butyrolactone scaffolds. The complete structures, including the absolute configurations of 1-3, were determined based on spectroscopic data and total syntheses. In methylthiazole tetrazolium (MTT) assays, 1 and 2 showed moderate cytotoxicity against P388 cells.

An interesting natural product chemistry aspect of Fragraea fragrans is that their fruits are richness with ursolic acid and its isomer oleanolic acid (3.05% of dried powder). As our continuous work on these inseparable structural isomeric triterpenes, this paper reports that 51.0% of inseparable 3-oxo-ursolic[3-oxo-oleanolic] acids and 48.6% of inseparable 3-acethyl-ursolic [3-acethyl-oleanolic] acids have already been made from those triterpenes as starting materials of the oxidized and acetylated compounds and evaluated their activity against P388 leukemia cells. The activity of 3-oxo-ursolic [3-oxo-oleanolic] acids with IC50 = 18.6 µg/mL exhibited three-fold more potent against P388 leukemia cell proliferations compared to ursolic [oleanolic] acids with IC50 = 53.5 µg/mL; while the 3-acethyl-ursolic [3-acethyl-oleanolic] acids with IC50 = 37.9 µg/mL showed two-fold more potent then their parent triterpenes (IC50 = 53.5 µg/mL) in the inhibition of P388 leukemia cell growth.

Ester derivatives of p-hydroxycinnamic compounds have high anticancer activity. However, the ester compounds usually easier to be decomposed than their amide derivates, so the ester compounds have a low potential to be applied as anticancer. In this research, the amide derivatives of caffeic and p-coumaric acids have been synthesized using o-tolylamine to give trans-N-(o-tolyl)caffeamide (5a) and trans-N-(o-tolyl)-p-coumaramide (5b), respectively. The products were characterized by FT-IR, 13C-NMR, and 1H-NMR methods. In the FT-IR spectrum, compound 5a showed absorption bands of N-H bond at 3236.55 cm−1 and 1533.41 cm−1 as stretching and bending vibrations, respectively; and compound 5b had absorption bands at 3267.41 cm−1 and 1527.82 cm−1. In the 13C-NMR spectrum, compound 5a gave 15 of peaks that representing 16 of carbons, and compound 5b gave 14 of peaks that were also representing 16 of carbons. In the 1H-NMR spectrum, the peak of N-H of compound 5a and compound 5b appeared at 8.57 ppm and 8.87 ppm, respectively. Activity assay results of both compounds against P388 leukemia murine cells indicated that both compounds have a high potential as anticancer, especially compound 5a. The compound 5a was more active than the analogous compounds which the previous synthezised.

Three novel multiflorane-type triterpenoids, 3α-p-nitrobenzoylmultiflora-7:9(11)-diene-29-benzoate (1), 3α-acetoxymultiflora-7:9(11)-diene-29-benzoate (2), and 3α-acetoxymultiflora-5(6):7:9(11)-triene-29-benzoate (3), along with two known related compounds 4 and 5 were isolated from the seeds of zucchini (Cucurbita pepo L). Their structures were determined on the basis of 1D and 2D NMR spectroscopy and HREIMS. Triterpenoids possessing a nitro group were not isolated previously.

One new abietane-type norditerpenoid, named militibetin A (1), was isolated from the dry roots of Salvia miltiorrhiza, along with two known diterpenoids, yunnannin A (2) and ferruginol (3). Their structures were established by means of extensive spectroscopic analyses. In vitro, compounds 1-3 were found to show cytotoxicities against selected cancer cells, including P-388, HONE-1, and HT-29, and gave ED(50) values in the range of 2.9-5.4 μg ml(- 1).

Two new C(13)-norisoprenoids, named lyratols E and F (1-2), were isolated from the whole plant of Solanum lyratum Thunb, and their structures were elucidated by extensive spectroscopic analyses. In vitro, two new compounds were found to show significant cytotoxicity against selected cancer cells including P-388 and HT-29.

Two prenylated flavones have been successfully isolated from the methanol extract of the heartwood Artocarpus scortechinii King. They were determined as artelastisin and artelastin. It has been reported that artelastisin and artelastin were obtained from Artocarpus elasticus. The cytotoxicity toward cell murine leukemia P-388 showed that artelastisin is active with IC50 3.0 µg/mL. In addition, artelastin is inactive with IC50 5.75 µg/mL. The structures of isolated compounds were determined based on spectroscopy data including UV, IR, 1H and 13C-NMR. These compounds are reported for the fist time from this plant. Keywords: Artocarpus scortechinii King, prenylated flavone, and cell murine leukemia P-388.

Four polyacetylenes related to petroformyne-1 were isolated from the marine sponge Petrosia sp. Their structures were determined on the basis of spectroscopic data and the modified Mosher analysis. They exhibit cytotoxic activity against P388 murine leukemia cells.

Boc-Trp-Leu hydrazide has been found to significantly inhibit growth of the L-1210 and P388 murine lymphocytic leukemias. A series of related tryptophan dipeptides were prepared and found to be devoid of such activity. The tryptophan dipeptides were most conveniently obtained employing the DCCI-NHS peptide bond-forming procedure.

Chemical investigations on the acetone and MeOH solubles of the soft coral Nephthea erecta have afforded five new sesquiterpenoids (1-5), one known sesquiterpene, kelsoene (6), and two known 19-oxygenated steroids (10 and 11). In addition, three unexpected artificial 19-oxygenated steroids (7-9) were obtained by letting 10 and 11 stand in CDCl(3) for prolonged periods of time. The structures of 1-9 were elucidated by extensive spectroscopic analyses, and their cytotoxicity against selected cancer cells was measured in vitro.

Chemical investigation of an extract of the marine sponge Phyllospongia papyracea, collected from the South China Sea, led to the isolation and identification of three new scalarane-type sesterterpenoids, compounds 1–3. Their structures were elucidated by spectroscopic methods, including 1D- and 2D-NMR as well as high-resolution ESI-MS experiments. (12α,16β)-12-Acetoxy-16-hydroxy-20,24-dimethyl-25-norscalar-17-en-24-one (1) was cytotoxic against the leukemia P388 cancer cell line, with an IC50 value of 5 μg/ml.

A series of tricyclic hydroquinones, incorporating a carbonyl group in the ortho position relative to the phenol function, were tested as inhibitors of oxygen uptake against the TA3 mouse carcinoma cell line and its multidrug-resistant variant TA3-MTX-R. The title compound, which proved to be the most active one, also exhibited low micromolar dose-dependent growth inhibition of the human tumor U937 cell line (human monocytic leukemia). A tentative structure-activity relationship is proposed for these substances. A comparison between the cytotoxicities of the title compound and 4,4-dimethyl-5,8-dihydroxynaphthalene-1-one, with their activities as inhibitors of oxygen uptake by the TA3-MTX-R cell line, is presented. Also, the inhibition of oxygen uptake by 6-(4-methylpent-3-enyl)-1,4-naphthoquinone was determined and compared with its reported cytotoxicity toward P-388 (murine lymphocytic leukemia), A-549 (human lung carcinoma), HT-29 (human colon carcinoma), and MEL-28 (human melanoma) cells. The inhibition of oxygen uptake by TA3-MTX-R cells is useful as a quick test for preliminary screening of possible anticancer activity.

Eight new nornardosinane sequiterpenoids, laevinols A-H (1-8), a new neolemnane sesquiterpenoid, laevinone A (9), and the previously known 6beta-acetyl-4beta,5beta-dimethyl-1(10)alpha-epoxy-2beta-hydroxy-7-oxodecalin (10) and 11,12-dihydroxy-6,10-eremophiladiene (11) were isolated from the methylene chloride solubles of the Formosan soft coral Lemnalia laevis. Their structures were elucidated by extensive spectroscopic analysis, and their cytotoxicity against selected cancer cells was measured in vitro.

Eight new xenia diterpenoids, blumiolide-A (1) (novel carbon skeleton), blumiolide-B (2), 9-deoxy-isoxeniolide-A (3), 9-deoxy-7,8-epoxy-isoxeniolide-A (4), 9-deacetoxy-7,8-epoxy-13-epi-xenicin (5), 9-deoxy-7,8-epoxy-xeniolide-A (6), blumiolide-C (7), and blumicin-A (8), were isolated from the methylene chloride solubles of the Formosan soft coral Xenia blumi. Their structures were elucidated by extensive spectroscopic analysis, and their cytotoxicity against selected cancer cells was measured in vitro.

A new cycloheptapeptide, phakellistatin 14, was isolated in 8.8 x 10(-7)% yield from Phakellia sp., a marine sponge from Chuuk, Federated States of Micronesia. The structure (1), cyclo-Phe-beta-OMe-Asp-Ala-Met(SO)-Ala-Ile-Pro, was elucidated by 1D and 2D NMR spectral analyses augmented by HRFABMS. The chirality of each amino acid unit was determined to be S using chiral HPLC methods. Phakellistatin 14 showed cancer cell growth inhibitory activity (ED(50) 5 microg/mL) against the murine lymphocytic leukemia P388 cell line.

A series of novel 3,5-bis(phenylmethylene)-1-(N-arylmaleamoyl)-4-piperidones 3 have been synthesized which displayed potent cytotoxicity towards human Molt 4/C8 and CEM T-lymphocytes as well as murine P388 and L1210 leukemic cells. In contrast, the related N-arylmaleamic acids 4 possessed little or no cytotoxicity in these four screens. Molecular modeling revealed certain interplanar and bond angles and interatomic distances which were perceived to contribute to the observed bioactivity as well as providing suggestions for future structural modifications of the piperidones 3. Evaluation of representative compounds in series 3 and 4 on the activity of human N-myristoyltransferase revealed that, at the maximum concentration utilized, namely 250 microM, only weak inhibiting properties were displayed by some of the compounds in series 4. Various members of series 3 and 4 were well tolerated in mice.

Fermentation of Pseudeurotium zonatum led to the isolation of the known cytochalasin G (1) and three new cytochalasins, X, Y, and Z (2-4). These four compounds are the only naturally occurring cytochalasins reported to date that contain an indole-substituted perhydroisoindol-1-one fused with an 11-membered macrocycle.

Six new cytotoxic dolabellane diterpenes, (1R*,12R*)-dolabella-4(16),7,10-triene-3,13-dione (1), (1R*,7R*,8S*,12R*)-dolabella-4(16),10-diene-7,8-epoxy- 3,13-dione (2), (1R*,10R*,11S*,12R*)-dolabella-4(16),7-diene-10,11-epoxy-3,13-dione (3), (1R*)-dolabella-4(16),7,11(12)-triene-3,13-dione (4), (1R*,3R*)-3-hydroxydolabella-4(16),7,11(12)-triene-3,13-dione (5), and (1R*,7R*)-7-hydroperoxydolabella-4(16),8(17),11(12)-triene-3,13-dione (6), have been isolated from the Formosan soft coral Clavularia inflata. The structures of compounds 1−6 were determined by 1D and 2D spectral analysis, and their cytotoxicity against selected cancer cells was measured in vitro.

(−)-4-Aza-4-deoxypodophyllotoxin ( 4 ) was synthesized from (−)-podophyllotoxin ( 1 ) through C-ring cleavage, Curtius rearrangement and intramolecular N -alkylation. Analogue 4 showed potent cytotoxicity against P388 leukemia cells.

Four new alkaloids, pterocellins C-F (1-4), have been isolated from the New Zealand marine bryozoan Pterocella vesiculosa. Structural elucidation was achieved through NMR spectroscopic and mass spectrometric analysis and comparison of spectroscopic data with that of the known compounds pterocellins A and B. The biological activities of 1-4 were assessed in a number of different assay systems and compared with those of pterocellins A and B.

Three new sesquiterpenoid isopropylidene derivatives, named solajiangxins H and I (1 and 2) and 7-hydroxylsolajiangxin I (3), were isolated from the whole plant of Solanum lyratum. Their structures were elucidated on the basis of integrated spectroscopic techniques, mainly HR-FAB-MS, 1D NMR, and 2D NMR ((1)H-(1)H COSY, HMQC, HMBC, and NOESY). In vitro, compounds 1-3 were found to show significant cytotoxicity against three cancer cells (P-388, HONE-1, and HT-29), and gave IC50 values in the range of 3.2-7.7 μM.

Seven novel withanolides, sinubrasolides A-G (1-7), have been isolated from the cultured soft coral Sinularia brassica. The structures of the new metabolites were determined by extensive spectroscopic analyses, and the absolute configuration of 1 was established by X-ray crystallographic analysis. The cytotoxicities of compounds 1-7 against a limited panel of cancer cell lines also were determined.

A bioassay-guided investigation of Gustavia hexapetala led to the isolation of a new cancer cell growth inhibitor designated gustastatin (1) and four previously known cancer cell growth inhibitors that included betulinic acid (2). The structures were assigned on the basis of analyses of HRMS combined with 1D and 2D NMR data. The structure of portentol (5) was confirmed by an X-ray crystal structure determination.

Convergent synthesis of an antitumor protective agent, ascofuranone, was accomplished by (1) preparation of the terpenoid side chain having a furanone moiety, (2) coupling the side chain with a protected phenol derivative, and (3) deprotection to regenerate the hydroxyl groups. This strategy was successfully applied to the synthesis of oxidized and cyclized analogs of ascofuranone. Some of the ascofuranone derivatives were found to inhibit the growth of P388 leukemia cells.

A novel natural sesquiterpene–dimer-type compound, named parviflorene A ( 1 ), was isolated from the extract of a tropical Zingiberaceous plant, Curcuma parviflora, collected in Thailand, and its structure was elucidated by spectral data. Parviflorene A ( 1 ) possesses an unprecedented unsymmetrical bis-cadinane skeleton and exhibited cytotoxic activity against murine leukemia P388 and B16 melanoma cells.

Suberitine A-D (1-4), four new bis-aaptamine alkaloids with two aaptamine skeleton units, 8,9,9-trimethoxy-9H-benzo[de][1,6]-naphthyridine and demethyl(oxy)-aaptamine, linked through a rare C-3-C-3' or C-3-C-6' σ-bond between the 1,6-naphthyridine rings, together with two known monomers 5 and 6, were isolated from the marine sponge Aaptos suberitoides. Their structures were elucidated using NMR spectroscopy. Compounds 2 and 4 showed potent cytotoxicity against P388 cell lines, with IC(50) values of 1.8 and 3.5 μM, respectively.

Chemical investigation of the Dongsha Atoll soft coral Lobophytum crassum has afforded four new cembranoids, crassumols A-C (1-3) and 13-acetoxysarcophytoxide (4). The structures of these isolated compounds were elucidated by extensive NMR and HRESIMS experiments. The cytotoxicity and anti-HCMV (Human cytomegalovirus) activities of 1-4 were evaluated in vitro. Compound 4 exhibited cytotoxicity against A-549 (human lung carcinoma) cell line with an ED(50) of 3.6 μg/mL.

A series of analogs of (R,R)-1,2-diaminocyclohexane dichloroplatinum(II) (DACH) containing stereochemically defined hydroxy groups and appropriate acidic leaving groups were synthesized and tested as antitumor agents. The (1α,2β,3α,4β)-1,4-dihydroxy-2,3-diaminocyclohexane analog showed the highest potency against P388 leukemia in mice. The results indicate that increasing the hydrophilicity of the platinum complex to a certain extent could improve the antitumor activity of the drug. It is also likely that the stereochemical disposition of the substituents on the cyclohexane ring affects the antitumor activity.

Synthetic methodologies for the preparation of substituted 5-nitro- and 5-aminoanthra[1,9-cd]-pyrazol-6(2H)-ones, 4 and 5 respectively, substituted with a basic side at N-2 and dioxy substitution in the A-ring, are reported. These compounds are essentially devoid of activity against in vitro L1210 leukemia and in vivo murine P388 leukemia.

The synthesis of a series of N-(2-chloroethyl)-N′-(9H-xanthen-9-yl)-N-nitrosoureas and N-(2-chloroethyl)-N′-(9H-thioxanthen-9-yl)-N-nitrosoureas is described. The title compounds were evaluated against NSCLCN6 L16 bronchial epidermoid carcinoma in vitro and some of them were found to be active. N-(2-chloroethyl)-N′-(2-methoxy-9H-xanthen-9-yl)-N-nitrosourea (8e) was active against leukemia P388 tumor system in mice. Synthese und pharmakologische Prufung von neuen 2-Chlorethylnitrosoharnstoffen Eine Reihe von neuen N-(2-chlorethyl)-N′-(9H-xanthen-9-yl)-N-nitrosoharnstoffen und N-(2-chlorethyl)-N′-(9H-thioxanthen-9-yl)-N-nitrosoharnstoffen wurde dargestellt. Die neuen Verbindungen wurden auf Aktivitat gegen NSCLCN6 L16 (Epidermoides Bronchialkarzinom) in vitro gepruft: einige erwiesen sich als wirksam. Verbindung 8e ist auch gegen das Leukamie P388-Tumorsystem in vivo wirksam.

A versatile and efficient synthetic route to 4-demethoxyanthracyclinones has been utilized in the preparation of a number of aglycons having 9-alkyl, 9-(hydroxylalkyl), or 9-carbamoyl substituents. Silver trifluoromethanesulfonate catalyzed coupling of these aglycons with various daunosamine derivatives has yielded a series of novel anthracyclines which have been evaluated as antitumor agents. 9-Alkylanthracyclines 22, 23, 33, and 34 have higher efficacy vs L-1210 leukemia than the parent 4-demethoxydaunorubicin (21), or the natural anthracyclines daunorubicin (1) and doxorubicin (2). 9-(Hydroxyalkyl) derivatives have in most cases high efficacy but are slightly less potent than 21. 9-Methyl analogue 22 has higher efficacy vs P388 leukemia than other anthracyclines tested, while 9-(hydroxymethyl) derivative 37 retains similar efficacy to anthracyclines 1, 2, and 21 but is considerably more potent. The N-substituted 9-carbamoylanthracyclines are devoid of antitumor activity.

Novel indolo[3, 2-b]quinolines (1d-g), introduced at the 7-position with an N-glycosylamino group, were prepared and thier antitumor activities against leukemia P388 in mice were examined. The N-Galactopyranosylamino derivative (1e) was a much more potent anti-leukemia compound (optimal dose = 25 mg/kg, T/C>333%, cure 5/6) than lead compound 1a.

Synthetic methodologies for the preparation of substituted 5-nitro- and 5-aminoanthra[1,9-cd]-pyrazol-6(2H)-ones, 4 and 5 respectively, substituted with a basic side at N-2 and dioxy substitution in the A-ring, are reported. These compounds are essentially devoid of activity against in vitro L1210 leukemia and in vivo murine P388 leukemia.

Five new chlorinated phenyl ethers, russuphelins B (2), C (3), D (4), E (5) and F (6) have been isolated from the mushroom Russula subnigricans Hongo, and their structures were elucidated by spectroscopic and chemical means. Russuphelins B (2), C (3) and D (4) exhibited cytotoxic activity in vitro against P388 leukemia cells.

A series of C-6-substituted methyl mitomycins was synthesized and evaluated for anticellular and antitumor activities. These novel compounds were prepared by Michael addition of various alcohols or thiols to 6-demethyl-7,7-(ethylenedioxy)-6,7-dihydro-6-methylidenemitosanes followed by treatment with NH3 or MeOH/K2CO3. Most compounds were potent against HeLa S3, and some of them showed superior activity to that of mitomycin C (MMC) against P388 leukemia and sarcoma 180 in mice. In addition, some compounds exhibited remarkable activity against MMC-resistant P388 in mice. FAB-MS spectra of these mitomycin derivatives showed the elimination of the C-6-methyl substituents from the mitomycin skeletons to form quinonemethides. Interestingly, treatment of 6-demethyl-6-[[(2-pyrimidinyl)thio]methyl ]mitomycin C (12v) with diethylamine afforded 6-demethyl-6-[(diethylamino)methyl]mitomycin C (31) in good yield. These results suggested that the C-6-substituted methyl mitomycins would have different biological character from that of MMC.

The ethanolic extract of the root bark of Melia azedarach exhibited cytotoxic activity against lymphocytic leukemia P388 cell lines in vitro. Systematic fractionation of the extract monitored by cytotoxic bioassay led to the isolation of two new azadirachtin-type limonoids, 1-tigloyl-3-acetyl-11-methoxymeliacarpinin (1) and 1-acetyl-3-tigloyl-11-methoxymeliacarpinin (2), together with three highly cytotoxic sendanin-type limonoids, 29-isobutylsendanin (3), 12-hydroxyamoorastin (4) and 29-deacetylsendanin (5). The acetylated derivatives of 4 also underwent cytotoxic bioassay.

Synthesis of several new 5-amino-substituted derivatives of 5-amino-6H-imidazo[4,5,1-de]-acridin-6-one bearing in the benzene ring OH, OCH3, CH3, tert-butyl, or OCH2O groups is described. 8-OH-substituted compounds or double-substituted 7-OH-10-OCH3 compounds demonstrated potent in vivo activity against murine P388 leukemia. The highest activity was exhibited by 5-[[2-[[2-(diethylamino)ethyl]amino]ethyl]amino]-8-hydroxy-6H- imidazo[4,5,1-de]-acridin-6-one (4c).

Various kinds of water-soluble quaternary salts of 2-(2'-oxoalkoxy)-9-hydroxyellipticines were synthesized in a search for compounds with potent antitumor activity and low toxicity. Some compounds exhibited more potent antitumor activities than elliptinium (1) and SUN 4599 (3). In particular, 2-(3'-methoxy-2'-oxopropanoxy)-9- hydroxy-5,11-dimethyl-6H-pyrido[4,3-b]carbazolium bromide (4d) showed potent antitumor activities against P388 leukemia, colon 26, and Lewis lung carcinoma.

Chemical investigation of the octocoral Sarcophyton ehrenbergi led to the isolation of six new cembranoids, (+)-12-carboxy-11Z-sarcophytoxide (1), (+)-12-methoxycarbonyl-11Z-sarcophine (3), ehrenberoxides A-C (4-6), and lobophynin C (2), along with two known compounds, (+)-sarcophytoxide (7) and (+)-sarcophine (8). The structures of these isolated metabolites were elucidated through extensive spectroscopic analyses, while the relative configuration of 1 was confirmed by X-ray diffraction analyses. The chemical evidence combined with spectroscopic and physical data suggested that the locations of the epoxide and the methyl carboxylate for lobophynin C should be exchanged. Moreover, metabolites 1-6 were evaluated in vitro for their cytotoxicity against selected cancer and normal cells lines, antiviral activity against human cytomegalovirus, and antibacterial activity against Salmonella enteritidis.

Vermixocins A and B, 3-(1'-hydroxy-3'-methylbutyl)- and 3-(1'-acetoxy-3'-methylbutyl)-11-hydroxy-4-methoxy-9-methyl-5H,7H- dibenzo[c,f][1,5]dioxocin-5-one, respectively, were isolated from the mycelium of Penicillium vermiculatum. Both metabolites showed cytotoxic effects on lympholeukemia cells P388.

Seven cytotoxic 3-alkylpyridine alkaloids, hachijodines A-G, have been isolated from two marine sponges of the genera Xestospongia and Amphimedon. Their structures were determined on the basis of spectral data. These alkaloids are moderately cytotoxic against P388 murine leukemia cells with IC(50) values of 1.0-2.3 microg/mL.

The isolation is reported of four new variants of the halichondrin B skeleton, very minor potently bioactive components from the Poecilosclerid sponge Lissodendoryx sp. These compounds were isolated in microgram quantities only from a collection of 1 tonne of sponge. The structural elucidations relied heavily on the use of capillary NMR spectroscopy and the application of an HSQC-DEPT overlay technique.

Six new linear peptides, pterulamides I-VI (1-6), were isolated from the fruiting bodies of a Malaysian Pterula species. The structures were elucidated by MS and 2D NMR experiments, and the absolute configurations of the constituent amino acids established using Marfey's method. The pterulamides are mainly assembled from nonpolar N-methylated amino acids and, most interestingly, have non-amino-acid N-terminal groups, among them the unusual cinnamoyl, (E)-3-methylsulfinylpropenoyl, and (E)-3-methylthiopropenoyl groups. Furthermore, pterulamides I-V are the first natural peptides with a methylamide C-terminus. Pterulamides I and IV are cytotoxic against the P388 cell line with IC50 values of 0.55 and 0.95 microg/mL (0.79 and 1.33 microM), respectively.

Twenty-six thiosemicarbazones (III-1–III-26) were synthesized via three steps starting from hydrazine hydrate and carbon disulfide. The testing of anticancer activity of these compounds in vitro against P-388, A-549, and SGC-7901 shows that compounds III-15 and III-16 possess a higher inhibitory ability for P-388 and SGC-7901. Further testing shows that the value of IC 50 of compound III-16 against SGC-7901 reaches to 0.032 μM.

Synthesis of the epimer of pericosine B from (-)-quinic acid was achieved. This synthesis involves some regioselective and stereoselective processes. The desired product showed lower cytotoxic activity in comparison with natural pericosine B against the P388 leukemia cell line. The result implies that the stereocenter of C-6 in natural pericosine B plays an important role in this activity.