Synthesis, growth inhibitory activity against tumor cells, and structure-activity relationship of CGK733 and its analogs.

CGK733 was reported as a compound that inhibited ATM/ATR kinase activities and blocked their checkpoint signaling pathways with great selectivity. However, this paper was subsequently retracted, and the truth about the activity of CGK733 remains unclear. We synthesized various analogs of CGK733 with a modification of the carboxylic acid moiety and/or the aniline derivative moiety to accumulate knowledge of the structure-activity relationship of this compound. Growth inhibitory activity of CGK733 and novel 35 analogs against HeLa S3 cells was evaluated, and the structure-activity relationship revealed that analogs with the 2-naphthyl or 4-fluorophenyl group instead of the benzhydryl group have activity comparable to CGK733 and that the 3-nitro group on the aniline moiety significantly affects the activity.

Okeanic acid-A, a trihydroxy fatty acid from the Okinawan cyanobacterium Okeania hirsuta.

Trihydroxy fatty acids are oxidative metabolites of polyunsaturated fatty acids isolated from plants, bacteria, fungi, and microalgae and have a variety of biological activities. In this study, a new trihydroxy fatty acid, okeanic acid-A (1), was isolated together with malyngic acid (2) and 15,16-dihydromalyngic acid (3) from the cyanobacterium Okeania hirsuta collected in Okinawa, Japan. The planar structure of 1 was elucidated by detailed analyses using high-resolution ESI-MS and 1D and 2D NMR spectroscopy. The absolute configurations of the hydroxy groups in 1 were determined unambiguously by chemical derivatisation and a modified Mosher's method. These cyanobacterial trihydroxy fatty acids (1-3) have identical configurations at their respective trihydroxy parts. Okeanic acid-A (1) showed mild growth-inhibitory activity against the marine diatom Nitzschia amabilis.

Potent antitumor effects of the conditioned medium of bone marrow-derived mesenchymal stem cells via IGFBP-4.

Cell transfer therapy using mesenchymal stem cells (MSCs) has pronounced therapeutic potential, but concerns remain about immune rejection, emboli formation, and promotion of tumor progression. Because the mode of action of MSCs highly relies on their paracrine effects through secretion of bioactive molecules, cell-free therapy using the conditioned medium (CM) of MSCs is an attractive option. However, the effects of MSC-CM on tumor progression have not been fully elucidated. Herein, we addressed this issue and investigated the possible underlying molecular mechanisms. The CM of MSCs derived from human bone marrow greatly inhibited the in vitro growth of several human tumor cell lines and the in vivo growth of the SCCVII murine squamous cell carcinoma cell line with reduced neovascularization. Exosomes in the MSC-CM were only partially involved in the inhibitory effects. The CM contained a variety of cytokines including insulin-like growth factor binding proteins (IGFBPs). Among them, IGFBP-4 greatly inhibited the in vitro growth of these tumors and angiogenesis, and immunodepletion of IGFBP-4 from the CM significantly reversed these effects. Of note, the CM greatly reduced the phosphorylation of AKT, ERK, IGF-1 receptor beta, and p38 MAPK in a partly IGFBP4-dependent manner, possibly through its binding to IGF-1/2 and blocking the signaling. The CM depleted of IGFBP-4 also reversed the inhibitory effects on in vivo tumor growth and neovascularization. Thus, MSC-CM has potent inhibitory effects on tumor growth and neovascularization in an IGFBP4-dependent manner, suggesting that cell-free therapy using MSC-CM could be a safer promising alternative for even cancer patients.

Nanohybrids of oxides nanoparticles-chitosan and their antimicrobial properties.

Growing international problem with pathogens acquiring resistance to antibiotics is the reason for the search for bactericidal substances against which microorganisms cannot become resistant. The aim of this study was to synthesize inorganic-organic nanohybrids and obtain materials with antimicrobial effects. Chitosan (CS) was deposited on nanocomposite carriers such as calcium oxide with titanium dioxide (CaO-TiO2), magnesium oxide with titanium dioxide (MgO-TiO2) and copper(II) oxide with titanium dioxide (CuO-TiO2). The efficiency of the process was examined at varying concentrations of chitosan and temperature. The parameters for nanohybrids synthesis were selected based on the highest amount of nano-chitosan deposited on the nanohybrids-for each carrier, the process conditions were as follows: chitosan solution at 5 g l-1and 20 °C. The materials were obtained using these parameters and were used for microbiological tests againstE. coliATCC 25922,S. aureusATCC 25923 andC. albicansATCC 10231. The growth inhibitory activity of the obtained materials was qualitatively defined. These results suggest that the synthesized nanohybrids and nanocomposites exhibit biostatic action. The material with the broadest effect was the CuO-TiO2-CS hybrid, which had biostatic properties against all tested strains at a minimal concentration of 1250µg ml-1. Further research is required to find eco-friendly, non-toxic, and more effective antimicrobials with a broad action to prevent the acquisition of resistance.

Development of Botanical Pesticides: Exploration on the Phenotype of Vestigial Wings of Insect Pests Induced by Plant Natural Products or Their Derivatives by Blocking Tyrosine Phosphorylation of Insulin Receptor 1.

Unlike faster-acting conventional insecticides, some botanical insecticides exhibit growth inhibitory activity against some insect pests. One of the distinguishing features of growth inhibitory activity appears to be in malformed moths with vestigial wings. However, the molecular mechanism underlying vestigial wings of insect pests induced by plant natural products or their derivatives is still elusive. In this work, based upon the phenotype of the vestigial wings of Mythimna separata Walker (as a model pest) induced by a podophyllotoxin derivative 2a (as a model compound), we found that compound 2a not only resulted in 22.1% of malformed moths with vestigial wings but also significantly decreased the fecundity of vestigial-winged female moths in the P generation; the trait of vestigial wings caused by 2a in the P generation can be inherited by the F1 generation; compound 2a may target insulin receptor 1 (InR1), suppress the InR1 mRNA level, and block InR1-pY1229 and InR1-pY1233/1234 phosphorylation levels in a tissue-specific manner "head/thorax/wing tissues". Notably, compound 2a can also induce the vestigial wings of Spodoptera frugiperda (another seriously harmful migratory lepidoptera pest). It is noteworthy that this insect insulin receptor can be used as a new kind of target receptors for the design of novel green insecticides.

Optimization of Osthole in the Lactone Ring: Structural Elucidation, Pesticidal Activities, and Control Efficiency of Osthole Ester Derivatives.

Here, we prepared a series of novel osthole-type ester derivatives modified in the lactone ring of osthole, which is isolated from Cnidium monnieri. The positions of H-3 and H-4 of the representative compound 4z were determined by a 1H-1H COSY spectrum. By opening the lactone ring of osthole, the double bonds at the C-3 and C-4 positions of diol 3 and esters 4a-4z, 4a', and 4b' were still retained as a Z configuration. That is, H-3 and H-4 of compounds 3 and 4a-4z, 4a', and 4b' were all in the cis relationship. The steric configurations of 4k, 4v, and 4z were further undoubtedly determined by single-crystal X-ray diffraction. Against Tetranychus cinnabarinus Boisduval, four aliphatic esters 4c (R = n-C3H7; LC50: 0.31 mg/mL), 4d (R = CH3(CH2)10; LC50: 0.24 mg/mL), 4a' (R = CH3(CH2)9; LC50: 0.28 mg/mL), and 4b' (R = CH3(CH2)12; LC50: 0.32 mg/mL) showed the most promising acaricidal activity, and compounds 4c, 4d, and 4a' also exhibited a potent control efficiency. Especially, compound 4d exhibited greater than fivefold acaricidal activity of the precursor osthole (LC50: 1.22 mg/mL). Against Mythimna separata Walker, compounds 4g, 4l, and 4m displayed 1.6-1.8-fold potent insecticidal activity of osthole. It demonstrated that the lactone ring of osthole is not necessary for the agricultural activities, thiocarbonylation of osthole was not beneficial for the agricultural activities, introduction of R as an aliphatic chain is vital for the acaricidal activity, notably, the length of the aliphatic chain is related to the acaricidal activity, 4d could be further studied as a lead acaricidal agent, and to the aromatic series, R containing the fluorine atom(s) is important for the insecticidal activity.

The antifeedant, insecticidal and insect growth inhibitory activities of triterpenoid saponins from Clematis aethusifolia Turcz against Plutella xylostella (L.).

BACKGROUND: The diamondback moth, Plutella xylostella (L.) (Lepidoptera: Plutellidae), is a global insect pest of crops, leading to a reduction of agricultural products in productivity and quality. Plant saponins are rich sources for the discovery of candidates to control insect pests. This study focused on discovery of triterpenoid saponins from Clematis aethusifolia Turcz and evaluation of their antifeedant, insecticidal and insect growth inhibitory activities against the 3rd instar larvae of P. xylostella. RESULTS: Seven triterpenoid saponins (1-7) were isolated for the first time from the n-BuOH extract of C. aethusifolia. Monodesmosides 1, 2, and 5 with a free 28-COOH group showed much higher antifeedant activity (DC50 were 733.67-844.77 µg mL-1 at 24 h, and 737.19-748.28 µg mL-1 at 48 h) than bidesmosides 3-4 and 6-7 (DC50 were 1284.35-2053.98 µg mL-1 at 24 h, and 1183.72-1990.96 µg mL-1 at 48 h). Similarly, monodesmosides 1, 2, and 5 (LC50 were 1462.78-1785.96 µg mL-1 ) showed stronger insecticidal activity than bidesmosides 3-4 and 6-7 (LC50 were 2219.22-3050.51 µg mL-1 ) against P. xylostella at 72 h. These results suggest the 28-COOH group is an important functional group for their antifeedant and insecticidal activity. Besides, monodesmosides 1, 2, and 5 showed insect growth inhibitory activity against P. xylostella through reduction of larval growth and percentage of pupation, associated with prolongation of larval and pupal stages. CONCLUSION: The present results provide evidence that triterpenoid saponins from C. aethusifolia, particularly those monodesmosidic saponins with a free 28-COOH group, have the potential to be developed as pesticides to control P. xylostella.

First Broad Screening of Allelopathic Potential of Wild and Cultivated Plants in Turkey.

Turkey has one of the richest plant diversities in the Mediterranean region. In the current literature, no broad screening has been conducted on the potential allelopathy of plants from Turkey. This study aimed to evaluate the allelopathic activity of a large number of plants from Turkey for the first time and to determine the species with significant plant growth inhibitory potentials by bioassay. Dried samples of different plant parts were collected from local herbalists. The sandwich method was used to evaluate the potential allelopathy of 126 medicinal plants belonging to 55 families. The results of lettuce radicle and hypocotyl growth for 10 and 50 mg sample treatment conformed to normal distribution. Significant inhibition on lettuce radicle elongation with 10 mg sample was observed in 40 species, out of which 27 species showed over 50% inhibitory activity. The results suggested that these species could contain potential inhibitory compounds against lettuce radicle or hypocotyl growth. The calyxes of Hibiscus sabdariffa (3.2% of control) and the seeds of Prunus dulcis (5.7% of control) showed the most potent growth inhibitory activity on lettuce radicle elongation. The potential plant growth inhibitory effects of these plants, together with the fruits of Rhus coriaria and seeds of Prunus mahaleb, have been reported in this study for the first time. All these plants are medicinal, and the results hereby presented provide essential information about the allelopathic effects of medicinal plants from Turkey.

Antibody Reactivity to Merozoite Antigens in Ghanaian Adults Correlates With Growth Inhibitory Activity Against Plasmodium falciparum in Culture.

BACKGROUND: Plasmodium falciparum uses a repertoire of merozoite-stage proteins for invasion of erythrocytes. Antibodies against some of these proteins halt the replication cycle of the parasite by preventing erythrocyte invasion and are implicated as contributors to protective immunity against malaria. METHODS: We assayed antibody reactivity against a panel of 9 recombinant antigens based on erythrocyte-binding antigen (EBA) and reticulocyte-like homolog (Rh) proteins in plasma from children with malaria and healthy adults residing in 3 endemic areas in Ghana using enzyme-linked immunosorbent assay. Purified immunoglobulin (Ig)G from adult plasma samples was also tested for invasion inhibition against 7 different P falciparum culture lines, including clinical isolates. RESULTS: Antibodies against the antigens increased in an age-dependent manner in children. Breadth of reactivity to the different antigens was strongly associated with in vitro parasite growth inhibitory activity of IgG purified from the adults. The strongest predictors of breadth of antibody reactivity were age and transmission intensity, and a combination of reactivities to Rh2, Rh4, and Rh5 correlated strongly with invasion inhibition. CONCLUSIONS: Growth inhibitory activity was significantly associated with breadth of antibody reactivity to merozoite antigens, encouraging the prospect of a multicomponent blood-stage vaccine.

Substrate and inhibitor selectivity, and biological activity of an epoxide hydrolase from Trichoderma reesei.

Epoxide hydrolases (EHs) are present in all living organisms and catalyze the hydrolysis of epoxides to the corresponding vicinal diols. EH are involved in the metabolism of endogenous and exogenous epoxides, and thus have application in pharmacology and biotechnology. In this work, we describe the substrates and inhibitors selectivity of an epoxide hydrolase recently cloned from the filamentous fungus Trichoderma reesei QM9414 (TrEH). We also studied the TrEH urea-based inhibitors effects in the fungal growth. TrEH showed high activity on radioative and fluorescent surrogate and natural substrates, especially epoxides from docosahexaenoic acid. Using a fluorescent surrogate substrate, potent inhibitors of TrEH were identified. Interestingly, one of the best compounds inhibit up to 60% of T. reesei growth, indicating an endogenous role for TrEH. These data make TrEH very attractive for future studies about fungal metabolism of fatty acids and possible development of novel drugs for human diseases.

Semisynthesis of Matrinic Acid/Alcohol/Ester Derivatives, Their Pesticidal Activities, and Investigation of Mechanisms of Action against Tetranychus cinnabarinus.

To discover new natural-product-based potential pesticides, 85 matrinic acid/alcohol/ester derivatives were synthesized by structural modifications of a quinolizidine alkaloid matrine. N-(4-Methyl)benzylmatrinyl n-decylate (76) and N-(2-chloro)benzylmatrinyl n-undecylate (86) exhibited greater than seven-fold more pronounced acaricidal activity than matrine against Tetranychus cinnabarinus; N-(2-chloro)benzylmatrinyl benzoate (80) showed the most promising insecticidal activity against Mythimna separata. The carboxyl group of matrinic acids and introduction of n-decyl/ n-undecylcarbonyl into matrinic alcohols were important for the acaricidal activity; introduction of alkyloxy into the carboxyl of matrinic acids and introduction of the electron-withdrawing groups on the N-benzyl of matrinic esters were necessary for the insecticidal activity. Through RT-PCR and qRT-PCR analysis, it was shown that the lactam ring of matrine was vital for action on VGSC; opening the lactam ring of matrine and the alkylcarbonyl of side-chain were two important factors for acting with α1, α2, and α4 nAChR subunits; α1, α2, α4, and ß3 subunits may be the target of action of compound 86 against T. cinnabarinus.

Re-engineering and synthesis of cytotoxic 2,3:7,8-di(alkylenedioxy)-extended analogs of quaternary sanguinarine chloride.

A method was developed to synthesize 2,3:7,8-di(alkylenedioxy)-extended analogs of quaternary sanguinarine chloride. 1-Bromo-2-bromomethyl-3,4-alkylenedioxy benzenes and 6,7-alkylenedioxynaphthalen-1-amines were synthesized first. Reactions to construct the target compounds with these two series of synthons involved alterations on a published method for synthesizing 2,3,7,8-tetraoxygenated derivatives of benzo[c]phenanthridinium, substituting benzyl bromides for benzoic aldehydes, prolonging the radical annulation time, and conducting N-methylation with formic acid and NaBH4. All the target compounds showed the same or better in vitro growth inhibitory activities against cancer cell lines compared with the positive compound. The structure activity relationship relevant to cytotoxicity and lipophilicity of the target compounds was produced.

Synthesis of Piperine Analogs Containing Isoxazoline/Pyrazoline Scaffold and Their Pesticidal Bioactivities.

In continuation of our program to discover new potential pesticidal agents, thirty-one piperine analogs containing isoxazoline/pyrazoline scaffold were prepared, and confirmed by infrared spectra, proton/carbon-13 nuclear magnetic resonance spectra, and high-resolution mass spectra. The structures of compounds VIIb and VIIIc were further determined by 1H-1H COSY spectra. Especially the configuration of compound VIIIc was unambiguously confirmed by single-crystal X-ray diffraction. Their pesticidal activities were evaluated against three serious and typically crop-threatening agricultural pests, Tetranychus cinnabarinus Boisduval (spider mite), Mythimna separata Walker (Oriental armyworm), and Plutella xylostella Linnaeus (diamondback moth). Compounds VIIIb and VIIIc exhibited greater than 40-fold more potent acaricidal activity than the lead compound piperine against T. cinnabarinus. Notably, compounds VIa-c exhibited more pronounced oral toxicity against P. xylostella than toosendanin; compounds VIb and VIc displayed more promising growth inhibitory activity against M. separata than toosendanin. It demonstrated that the methylenedioxy and isoxazoline scaffolds were important for the oral toxicity and growth inhibitory activity against P. xylostella and M. separata, respectively; the ethylenedioxy and isoxazoline scaffolds were vital for the acaricidal activity against T. cinnabarinus. Moreover, compounds VIb, VIIf, and VIIIc showed very low toxicity against NRK-52E cells.

Identification and Growth Inhibitory Activity of the Chemical Constituents from Imperata Cylindrica Aerial Part Ethyl Acetate Extract.

Imperata cylindrica (L.) Raeusch. (IMP) aerial part ethyl acetate extract has anti-proliferative, pro-apoptotic, and pro-oxidative effects towards colorectal cancer in vitro. The chemical constituents of IMP aerial part ethyl acetate extract were isolated using high-performance liquid chromatography (HPLC) and identified with tandem mass spectrometry (ESI-MS/MS) in combination with ultraviolet-visible spectrophotometry and 400 MHz NMR. The growth inhibitory effects of each identified component on BT-549 (breast) and HT-29 (colon) cancer cell lines were evaluated after 48/72 h treatment by MTT assay. Four isolated compounds were identified as trans-p-Coumaric acid (1); 2-Methoxyestrone (2); 11, 16-Dihydroxypregn-4-ene-3, 20-dione (3); and Tricin (4). Compounds (2), (3), and (4) exhibited considerable growth inhibitory activities against BT-549 and HT-29 cancer cell lines. Compounds (2), (3), and (4) are potential candidates for novel anti-cancer agents against breast and colorectal cancers.

Synthesis of New Glycosylated Flavonoids with Inhibitory Activity on Cell Growth.

Natural flavonoids and xanthone glycosides display several biological activities, with the glycoside moiety playing an important role in the mechanism of action of these metabolites. Herein, to give further insights into the inhibitory activity on cell growth of these classes of compounds, the synthesis of four flavonoids (5, 6, 9, and 10) and one xanthone (7) containing one or more acetoglycoside moieties was carried out. Acetyl groups were introduced using acetic anhydride and microwave irradiation. The introduction of one or two acetoglycoside moieties in the framework of 3,7-dihydroxyflavone (4) was performed using two synthetic methods: the Michael reaction and the Koenigs-Knorr reaction. The in vitro cell growth inhibitory activity of compounds 5, 6, 7, 9, and 10 was investigated in six human tumor cell lines: A375-C5 (malignant melanoma IL-1 insensitive), MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer), U251 (glioblastoma astrocytoma), U373 (glioblastoma astrocytoma), and U87MG (glioblastoma astrocytoma). The new flavonoid 3-hydroxy-7-(2,3,4,6-tetra-O-acetyl-ß-glucopyranosyl) flavone (10) was the most potent compound in all tumor cell lines tested, with GI50 values < 8 µM and a notable degree of selectivity for cancer cells.

Design, Synthesis and Bioactivity Evaluation of Novel ß-carboline 1,3,4-oxadiazole Derivatives.

A series of novel ß-carboline 1,3,4-oxadiazole derivatives were designed and synthesized, and the in vitro cytotoxic activity against Sf9 cells and growth inhibitory activity against Spodoptera litura were evaluated. Bioassay results showed that most of these compounds exhibited excellent in vitro cytotoxic activity. Especially, compound 37 displayed the best efficacy in vitro (IC50 = 3.93 µM), and was five-fold more potent than camptothecin (CPT) (IC50 = 18.95 µM). Moreover, compounds 5 and 37 could induce cell apoptosis and cell cycle arrest and stimulate Sf-caspase-1 activation in Sf9 cells. In vivo bioassay also demonstrated that compounds 5 and 37 could significantly inhibit larvae growth of S. litura with decreasing the weight of larvae and pupae. Based on these bioassay results, compounds 5 and 37 emerged as lead compounds for the development of potential insect growth inhibitions.

Six scalemic mixtures of 6-monosubstituted dihydrobenzophenanthridine alkaloids from Chelidonium majus and optically active structures of enantiomers.

Six pairs of previously undescribed 6-monosubstituted dihydrobenzophenanthridine alkaloids were separated as corresponding six scalemic mixtures from the aerial part of Chelidonium majus. The elucidation for the 2D structures of these alkaloids was achieved using regular spectroscopic and chemical methods. The assignment of scalemic-mixture nature was achieved using combined examinations of their NMR data, CD spectra, calculation of specific rotations, and chiral HPLC profiles. The identification for the relative configurations of alkaloids possessing two asymmetric carbons directly connected up by a rotatable sp3-sp3 carbon-carbon single bond was significantly facilitated by discussing the erythro and threo relative configurations defined by the mutuality of the orders of decreasing steric hindrances between the two sets of ligands linked to the two chiral centers. Two scalemic mixtures were assigned as (1'R,6R/1'S,6S)- and (1'S,6R/1'R,6S)-1-(dihydrochelerythrine-6-yl)ethanols, two as (1'R,6R)/(1'S,6S)- and (1'S,6R)/(1'R,6S)-1-(dihydrosanguinarine-6-yl)ethanols, one as (±)-ethyl 2-(dihydrosanguinarine-6-yl)acetate, and one as (±)-ethyl dihydrosanguinarine-6-carboxylate, respectively. The resolution of three scalemic mixtures was achieved and the absolute configurations of the three pairs of enantiomers were assigned via time-dependent Density Functional Theory calculations of electronic circular dichroism (ECD) data. The assignment for the absolute configurations of the other three scalemic mixtures was achieved via a chiral HPLC-UV/CD method plus analyzing their ECD data. The findings of this paper demonstrated that the relevant biochemical reactions concerning the construction of these 6-monosubstituted dihydrobenzophenanthridine alkaloids in the test plant are very nonselective. Scalemic mixture of (1'R,6R)/(1'S,6S)-1-(dihydrosanguinarine-6-yl)ethanol exhibited biological activity. It inhibited the growth of human MDA-MB-231 cell line at a moderate level with IC50 value of 5.12 µM.

Tamaractam, a New Bioactive Lactam from Tamarix ramosissima, Induces Apoptosis in Rheumatoid Arthritis Fibroblast-Like Synoviocytes.

Chemical investigation of Tamarix ramosissima Ledeb, a traditional herbal medicine used for rheumatoid arthritis (RA) treatment in northwest China, led to the discovery of a new phenolic aromatic rings substituted lactam, tamaractam (1), together with the previously reported compounds cis-N-feruloyl-3-O-methyldopamine (2) and trans-N-feruloyl-3-O-methyldopamine (3). The structures of the compounds were determined by high resolution electrospray ionization mass spectroscopy (HRESIMS) and 1D and 2D-NMR experiments, as well as comparison with the literature data. The effects of the three compounds on the viability of RA fibroblast-like synoviocytes (RA-FLS) were assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Pro-apoptosis effect of compound 1 in RA-FLS was further investigated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, activated caspase-3/7 level assessment using luminescence assay, and sub-G1 fraction measurement using flow cytometry. It was found that these three compounds displayed variable proliferation inhibitory activity in RA-FLS, and compound 1 exhibited the strongest effect. Compound 1 could remarkably induce cellular apoptosis of RA-FLS, increase activated caspase-3/7 levels, and significantly increase sub-G1 fraction in the cell cycle. The results suggested that compound 1 may inhibit the proliferation of RA-FLS through apoptosis-inducing effect, and these compounds may contribute to the anti-RA effect of T. ramosissima.

Research progress on the chemicals with cancer stem cell growth inhibitory activity / 中国生化药物杂志

Cancer stem cells play a crucial role in tumors'invasion, metastasis, recurrence and drug resistance.Investigation on the chemicals with tumor stem cell growth inhibitory activity has been greatly highlighted in the field of anti-tumor drug discovery.This paper briefly reviews the recent progress of chemical investigations on substances with tumor stem cell growth inhibitory activity , aiming to give readers a reference on anti-tumor drug discovery.

Study on chemical constituents of sponge Mycale sp.from the South China Sea / 药学实践杂志

Objective To investigate the chemical constituents of marine sponge Mycale sp.collected from the South China Sea.Methods The ethyl acetate extract of the marine sponge Mycale sp.was separated and purified by repeated column chromatography on silica gel, Sephadex LH-20 and reversed-phase high-performance liquid chromatography (RP-HPLC).The structures of these compounds were identified by means of various modern spectroscopic techniques and comparison with their physicochemical properties to reported data.The tumor cell growth inhibitory activities of these compounds against human breast cancer cell lines MCF-7 and human lung cancer cell lines PC9 were tested by Cell Counting Kit-8 (CCK-8) method.Results Ten compounds were isolated and identified as cyclo-(Pro-Ile)(1),cyclo-(Pro-Leu)(2),cyclo-(Ile-Leu)(3),cyclo-(Phe-Pro)(4),cyclo-(Phe-Val)(5),cyclo-(Phe-Leu)(6),cyclo-(Phe-Ile)(7), 2′-deoxythymidine (8), thymine (9), 5-hydroxy-3,4-dimethyl-5-pentyl-2(5H)-furanone (10).These compounds showed weak tumor cell growth inhibitory activities toward cells MCF-7 and PC9 in vitro.Conclusion Compounds 1, 2, 4, 5, 6, 7 and 10 were isolated from the sponge Mycale sp.for the first time.It is the first time to report the antitumor activity evaluation for compounds 1~10.