CNS Cancer Cell Lines Research Articles

CNS Cancer Cell Line Cytotoxicity Profiles of Some 2, 6, 9-Substituted Purines: A Comparative Five-Dose Testing Study

The five dose comparative CNS Cancer Cell Line cytotoxicity profiles of N9-[4'-Chloro-2'-butynyl-1'-yl]-2,6- dichloropurine 1, Bis- 6,9-[4'-chloro-2'-butynyl-1'-yl]-thioguanine 2, Bis- 6,9-[4'-chloro-2'-butynyl-1'-yl]-mercaptopurine 3, Bis-6,9-[[o-(chloromethyl)phenyl]methyl]-thioguanine 4, Bis-6,9-[[o-(chloromethyl)phenyl]methyl]-mercaptopurine 5, 6-[4'-chloro-2'-butynyl-1'-yl]-thioguanine 6, and N9-[4'-Chloro-2'-butynyl-1'-yl]-6-(4-methoxyphenyl)purine 7 are presented in this communication. These compounds were evaluated for cytotoxic activity against NCI-60 DTP human tumor cell line five dose screen. All the unsaturated highly lipophilic substituents as expected contributed for the excellent CNS cancer cell line cytotoxicity, GI50 values 4-7 μM. Further, the thioguanine, mercaptopurine, and 6-phenylpurine are identified as the potential candidates for the CNS active cancer drug development and to cross the blood brain barrier. Keywords: CNS, prostates, Cancer, leukemia, 60-cell lines, chemotherapeutic agents, breast cancer, metabolic pathways, proliferation, taxanes

Antineoplastic agents. 548. Synthesis of iodo- and diiodocombstatin phosphate prodrugs.

Toward the objective of designing a structurally modified analogue of the combretastatin A-4 phosphate prodrug (1b) with the potential for increased specificity toward thyroid carcinoma, synthesis of a series of iodocombstatin phosphate (11a-h) and diiodocombstatin phosphate prodrugs (12a-h) has been accomplished. The diiodo series was obtained via 8a and 9c from condensation of 4 and 6, and the iodo sequence involved a parallel pathway. Both series of iodocombstatins were found to display significant to powerful inhibition of the growth of a panel of human cancer cell lines and of the murine P388 lymphocytic leukemia cell line. Of the diiodo series, 12a was also found to markedly inhibit growth of pediatric neuroblastoma, and monoiodocombstatin 9a strongly inhibited HUVEC growth. Overall, the strongest activity was found against the breast, CNS, leukemia, lung, and prostate cancer cell lines and the least activity against the pancreas and colon lines. Parallel biological investigations of tubulin interaction, antiangiogenesis, and antimicrobial effects were also conducted.

Pharmacophore, QSAR, and ADME based semisynthesis and in vitro evaluation of ursolic acid analogs for anticancer activity

In the present work, QSAR models for predicting the activities of ursolic acid analogs against human lung (A-549) and CNS (SF-295) cancer cell lines were developed by a forward stepwise multiple linear regression method using a leave-one-out approach. The regression coefficient (r(2)) and the cross-validation regression coefficient (rCV(2)) of the QSAR model for cytotoxic activity against the human lung cancer cell line (A-549) were 0.85 and 0.80, respectively. The QSAR study indicated that the LUMO energy, ring count, and solvent-accessible surface area were strongly correlated with anticancer activity. Similarly, the QSAR model for cytotoxic activity against the human CNS cancer cell line (SF-295) also showed a high correlation (r(2) = 0.99 and rCV(2) = 0.96), and indicated that dipole vector and solvent-accessible surface area were strongly correlated with activity. Ursolic acid analogs that were predicted to be active against these cancer cell lines by the QSAR models were semisynthesized and characterized on the basis of their (1)H and (13)C NMR spectroscopic data, and were then tested in vitro against the human lung (A-549) and CNS (SF-295) cancer cell lines. The experimental results obtained agreed well with the predicted values.

Synthesis and evaluation of anticancer activity of some novel 6-aryl-2-(p-sulfamylphenyl)-pyridazin-3(2H)-ones

A series of novel pyridazinone derivatives bearing benzenesulfonamide moiety (2a-h) has been synthesized by the condensation of appropriate aroylacrylic acid and 4-hydrazinobenzenesulfonamide hydrochloride in ethanol. Five derivatives (2a, 2b, 2d, 2g and 2h) were evaluated for their anticancer activity toward human cancer cell lines by the National Cancer Institute. The 2h showed remarkable activity against SR (leukemia) and NCI-H522 (non-small cell lung) with a GI(50) value of less than 0.1 μM. It also displayed good activity against leukemia (CCRF-CEM, HL-60 (TB), K-562, MOLT-4, RPMI-8226), non-small cell lung cancer (NCI-H460), colon (HCT-116, HCT-15, HT29, KMI2, SW-620), CNS (SF-295), melanoma (MALME-3M, M14, MDA-MB-435 SK-MEL-5), ovarian (OVCAR-3, NCI/ADR-RES) and breast (MCF7) cancer cell lines with a GI(50) less than 1.0 μM. The acute toxicity study of 2h indicated that it is well tolerated intra-peritoneally (400 mg/kg) by athymic nude mice. The 2h may possibly be used as lead compound for developing new anticancer agents.

Synthesis and biological evaluation of novel isoellipticine derivatives and salts

Synthesis of novel 7-substituted isoellipticines and isoellipticinium salts is described, with optimisation of routes, representing a new class of anti-cancer agent. Initial assessment of biological activity using a topoisomerase II decatenation assay and NCI screening highlighted strong anti-cancer activity, further developed in a panel of isoellipticinium salts. Interestingly, low correlation between results of the topoisomerase II decatenation assay and NCI screen throughout the panel suggest that topo II is not the most important biological target with respect to anti-cancer activity in this new class of compounds. Results also suggest that solubility is not the limiting factor in activity of the isoellipticinium salts. Overall, 20 novel ellipticine analogues were prepared and full anti-cancer profiling was completed for 13 isoellipticine derivatives and salts. Two compounds display significant specificity towards CNS cancer cell lines and are lead compounds for future development.

Fused Thiopyrano[2,3-d]thiazole Derivatives as Potential Anticancer Agents

rel-(5aR,11bR)-3,5a,6,11b-tetrahydro-2H,5H-chromeno[4′,3′:4,5]thiopyrano[2,3-d][1,3]thiazol-2-ones formed by the stereoselective Knoevenagel-hetero-Diels-Alder reaction were functionalized at the nitrogen in position 3 via reactions of alkylation, cyanoethylation, and acylation. The synthesized compounds were evaluated for their anticancer activity in NCI60 cell lines. Among the tested compounds, 3f was found to be the most active candidate with the greatest influence on leukemia, non-small cell lung cancer, colon cancer, CNS cancer, melanoma, prostate cancer, and breast cancer subpanel cell lines with GI50 values over a range of 0.37–0.67 μM.

Synthesis and biological activity of novel N-cycloalkyl-(cycloalkylaryl)-2-[(3-R-2-oxo-2 H-[1,2,4]triazino[2,3- c]quinazoline-6-yl)thio]acetamides

In this paper the novel N-cycloalkyl-(cycloalkylaryl)-2-[(3-R-2-oxo-2 H-[1,2,4]triazino[2,3- c]quinazoline-6-yl)thio]acetamides synthesis by aminolysis of activated by thionyl chloride or carbonyldiimidazole [(3-R-2-oxo-2 H-[1,2,4]triazino[2,3- c]quinazolin-6-yl)-thio]acetic acids and alkylation of the 3-R-6-thio-6,7-dihydro-2 H-[1,2,4]triazino[2,3- c]quinazoline-2-ones potassium salts with N-cycloalkyl-(cycloalkylaryl)-2-chloroacetamides are proposed. The structures of compounds are determined by 1H, 13C NMR, LC-MS and EI-MS analysis. The in vitro anticancer, antibacterial activity and Photobacterium leiognathi Sh1 bioluminescence inhibition of synthesized compounds were revealed. SAR results were discussed. Compound 4. 10 was found to be the most anticancer active one, selectively influenced on the non-small cell lung and CNS cancer cell lines, especially on the HOP-92 (log GI 50 = −6.01) and U251 (log GI 50 = −6.00).

Synthesis of Tetrahydronaphthalene Lignan Esters by Intramolecular Cyclization of Ethyl p-Azidophenyl-2-phenylalkanoates and Evaluation of the Growth Inhibition of Human Tumor Cell Lines

Intramolecular cyclization via nitrenium ion of 2-phenylpentanoic/2-phenylbutanoic acid esters with a terminal p-azidophenyl group gives direct access to tetrahydronaphthalene lignan esters. The p-azidophenyl-substituted butanoate led to an ethyl spirodienone carboxylate, while its homologue pentanoate gave ethyl 4-(4-aminophenyl)-1,2,3,4-tetrahydronaphthalene-1-carboxylate in good yield. In contrast, the m-azidophenyl-substituted esters suffered aromatic nucleophilic addition of trifluoromethanesulfonate. X-ray crystallography established unequivocally the end products structure, and density functional theory studies were performed to rationalize the cyclization outcome. Reaction intermediates and end products were evaluated for their capacity to inhibit in vitro growth of the cell lines MCF-7 (breast cancer), NCI-H460 (lung cancer), SF-268 (CNS cancer), and UACC-62 (melanoma). Growth inhibition of breast, lung, and CNS cancer cell lines was observed with the spirodienone carboxylate, the m-nitrophenylalkyl iodides, and p-phenyl-substituted elongated ethyl esters, namely, the p-nitrophenylpentanoate and p-aminophenylbutanoate, with the latter being also effective on the melanoma cell line.

Identification of Chrysoplenetin from Vitex negundo as a Potential Cytotoxic Agent against PANC‐1 and a Panel of 39 Human Cancer Cell Lines (JFCR‐39)

Human pancreatic cancer is known to be the most deadly disease with the lowest 5-year survival rate and is resistant to well known conventional chemotherapeutic drugs in clinical use. Screening of medicinal plants from Myanmar utilizing antiausterity strategy led to the identification of Vitex negundo as one of the medicinal plants having potent preferential cytotoxic activity against PANC-1 human pancreatic cancer cells. Bioactivity-guided phytochemical investigation led to the isolation of chrysoplenetin (1) and chrysosplenol D (2) as the active constituents with a PC(50) value of 3.4 μg/mL and 4.6 μg/mL, respectively, against PANC-1 cells. Both these compounds induced apoptosis-like morphological changes in PANC-1 cells. Chrysoplenetin was further tested against a panel of 39 human cancer cell lines (JFCR-39) at the Japanese Foundation for Cancer Research, and 25 cell lines belonging to lung, breast, CNS, colon, melanoma, ovarian, prostate cancer and stomach cancer cell lines were found to be highly sensitive to chrysoplenetin at a submicromolar range. In the JFCR-39 panel, lung NCI-H522, ovarian OVCAR-3 and prostate PC-3 cells were found to be most sensitive with GI(50) of 0.12, 0.18 and 0.17 μm, respectively. The COMPARE analysis suggested that the molecular mode of action of chrysoplenetin was unique compared with the existing anticancer drugs.

Activation of caspases and poly (ADP-ribose) polymerase cleavage to induce apoptosis in leukemia HL-60 cells by Inula racemosa

Inula racemosa Hook.f. commonly known as Pushkarmula ( Compositae) has been used as a traditional drug in India, China and Europe. In the present study, 95% ethanolic extract of roots and its fractions ( n-hexane, chloroform, n-butanol and aqueous) were evaluated for in vitro cytotoxicity against cancer cell lines of colon, ovary, prostate, lung, CNS and leukemia. The n-hexane fraction containing alantolactone and isoalantolactone as its major constituents was further studied for its mode of action in HL-60 cells. The lowest IC 50 value of n-hexane fraction was 10.25 μg/ml for Colo-205, a colon cancer cell line whereas, 17.86 μg/ml was the highest IC 50 value observed against CNS cancer cell line SF-295. Further studies on HL-60 cells treated with n-hexane fraction at 10, 25 and 50 μg/ml for 6 h, revealed that it induces apoptosis through intrinsic as well as extrinsic pathways by generating reactive oxygen species (ROS) intermediates. Mitochondrial dysfunction prompted the release of cytochrome c, translocation of pro-apoptotic protein (Bax), activation of caspase cascade, resulting in the cleavage of some specific substrates for caspase-3 such as poly (ADP-ribose) polymerase (PARP), which eventually leads to apoptosis. The results of present study strongly support further research and development of bioactive constituents from Inula racemosa as potential anticancer agent with possible therapeutic implication.

In vitro cytotoxicity of extracts and fractions of Calotropis procera (Ait.) roots against human cancer cell lines

This study was designed to determine the antiproliferative activity of three extracts (alcoholic, hydro-aqueous and aqueous) and their fractions from the root part of Calotropis procera using human oral (KB) and central nervous system (SNB-78) cancer cell lines as a model system. KB and SNB-78 cells were cultured in the presence of extracts and fractions at various concentrations (10, 30 and100 μg/ml) for 48 h, and the percentage of cell viability was evaluated by the sulforhodamine-B (SRB) assay. Our result indicates that out of the three extracts of C. procera (root), alcoholic extract had shown greater potential for growth inhibition followed by hydro-aqueous extract at three different concentration of 10 μg/ml, 30 μg/ml and 100 μg/ml in a dose-dependent manner, whereas aqueous extract was found to be least active against both oral and CNS human cancer lines. On evaluation of the fractions prepared from alcoholic and hydro-aqueous extracts, it was observed that chloroform fraction from alcoholic extract was antiproliferative for oral (KB) cancer cell line and n-butanol fraction from alcoholic extract was antiproliferative for CNS cancer cell line than remaining fractions at three different concentration of 10 μg/ml, 30 μg/ml, 100 μg/ml in a dose-dependent manner. Thus, our result indicates that the root part of C. procera possess in vitro cytotoxicity against oral and CNS human cancer cell lines. Further investigations are required to obtain the clinically important lead molecules for the drug development. Key words: Cytotoxicity, Calotropis procera, fractions, human cancer cell line extracts

Synthesis of new spiroindolinones incorporating a benzothiazole moiety as antioxidant agents

3 H-Spiro[1,3-benzothiazole-2,3′-indol]-2′(1′ H)-ones 3a– c and 4a– e were synthesized from treating the 5-substituted 1 H-indole-2,3-diones with 2-aminothiophenol in ethanol. The structures were confirmed by elemental analyses, spectrometry (IR, 1H NMR, 13C NMR, HSQC-2D and LCMS-APCI) and single crystal X-ray analysis. The new compounds were screened for their antioxidant activities such as the Fe 3+/ascorbate system induced inhibition of lipid peroxidation (LP) in liposomes, trolox equivalent antioxidant capacity (TEAC), scavenging effect on diphenylpicryl hydrazine (DPPH ), and reducing power. These compounds showed potent scavenging activities against DPPH and 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS + ) radicals, reducing powers, and strong inhibitory capacity on lipid peroxidation. Compound 4a incorporating methyl both at R 1 and R 2 was found to be the most potent antioxidant described in this study. Compounds 3b and 4b were selected as representative compounds by the National Cancer Institute for screening against anticancer activity and these compounds were found to be cytotoxic against CNS cancer cell line SNB-75 in the primary screen.

Synthesis and Anticancer Activity of Novel Nonfused Bicyclic Thiazolidinone Derivatives

A series of new 2-{4-oxo-2-[(4-oxothiazolidin-2-ylidene)-hydrazono]-thiazolidin-5-yl}-N-arylacetamides ( 4a–e ), 5-(2-oxo-2-aryl-ethyl)-2-[(4-oxothiazolidin-2-ylidene)-hydrazono]-thiazolidine-4-ones ( 5a–d ), 2-(4-oxo-2-[(2-oxothiazolidin-4-ylidene)-hydrazono]-thiazolidin-5-yl)-N-arylacetamides ( 7a–e ), and 5-(2-oxo-2-aryl-ethyl)-2-[(2-oxothiazolidin-4-ylidene)-hydrazono]-thiazolidine-4-ones ( 8a–d ) have been synthesized starting from 2-thioxothiazolidin-4-one and 4-thioxothiazolidin-2-one through a multistep reaction sequence. 2-Thioxothiazolidin-4-one was alkylated via the intermediate formation of the triethylammonium salt 1 by ethyl chloroacetate. Compound 2 and 4-thioxothiazolidin-2-one reacted with thiosemicarbazides to give the 1-(4-thiazolidinone-2-ylidene)-4-R-thiosemicarbazones ( 3a,b ) and 1-(2-thiazolidinone-4-ylidene)thiosemicarbazones ( 6a,b ), respectively. Following [2+3]-cyclization of thiazolidinone-substituted thiosemicarbazones ( 3a,b and 6a,b) with N-arylmaleimides and aroylacrylic acids as equivalents of dielectrophilic synthon [C2]2 +, novel non-fused bicyclic thiazolidinones ( 4a–e, 5a–d, 7a–e, 8a–d ) were synthesized. The structures of the new compounds ( 4a–e, 5a–d, 7a–e, 8a–d ) were established on the basis of their elemental analysis and 1H NMR and mass spectral data. Eight of the synthesized compounds were tested, and three of them displayed different levels of antitumor activity. The most efficient antitumor agent—2-{4-oxo-3-furylmethyl-2-[(4-oxothiazolidin-2-ylidene)-hydrazono]-thiazolidin-5-yl}-N-4-chlorophenylacetamide ( 4d ) was found to be active against leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate, and breast cancer cell lines with mean lgGI50 and lgTGI values of –5.35 and –4.78, respectively.

Lipid Peroxidation, Cyclooxygenase Enzyme and Tumor Cell Proliferation Inhibitory Lignans from Justicia Species

The genus Justicia is a rich source of lignans, especially aryl naphthalide lignans. Lignans are biologically active phytochemicals, and are reported to possess antiplatelet, antiviral, anti-tumor, antidepressant, and insect antifeedant activities. In the present study, we report lipid peroxidation (LPO), cyclooxygenase (COX-1 and −2) enzyme and tumor cell proliferation inhibitory activities of lignans, namely, lariciresinol (1), isolariciresinol (2), neesiinoside A (3), justirumalin (4), justalakonin (5), justicidin G (6), sesamin (7), sesamolin (8), jusmicranthin methyl ether (9), taiwanin E methyl ether (10), lignan J1 (11), jusneesiinol (12), jusmicranthin ethyl ether (13), tiruneesiin (14), justicidin E (15) and simplexolin (16). Lignans 1 and 2 were isolated from J. tranquebariensis, 3, 4, 6, 9, 10, 11, 12, 13 and 14 from J. neesii Ramamoorthy, 5 from J. purpurea and 7, 8, 15 and 16 from J. orbiculata. Among the lignans assayed, 1, 2, 12 and 14 showed 79.6, 86.2, 90.8 and 95.9% and 3 41.3% inhibition of LPO at 25 μg/mL. The lignans 4, 9 and 16 inhibited COX-2 enzyme by 67.2, 73.0 and 72.8%, respectively, when tested at 25 μg/mL. Similarly, lignans 3, 4, 10, 11 and 15 inhibited COX-1 enzyme by 59.9, 89.2, 69.6, 73.9, and 80.1%, respectively, at 25 μg/mL. When assayed at 25 μg/mL, 4 inhibited human stomach and breast cancer cell lines by 42.8 and 42.1%, respectively. Also, at 25 μg/mL the lignan 7 inhibited the growth of CNS, lung and breast cancer cell lines by 50.0, 41.3, and 42.0 %, respectively, and 15 inhibited the proliferation of lung, breast and colon cell lines by 40–53%.

Synthesis of novel thiazolone-based compounds containing pyrazoline moiety and evaluation of their anticancer activity

To examine the anticancer activity several novel thiazolone-based compounds containing 5-aryl-3-phenyl-4,5-dihydro-1 H-pyrazol-1-yl framework were obtained. Reaction of 5-aryl-3-phenyl-4,5-dihydropyrazole with 4-thioxo-2-thiazolidinone or 2-carbethoxymethylthio-2-thiazoline-4-one yielded starting 4- ( 1 and 2) or 2-substituted ( 11 and 12) thiazolones which were utilized in Knoevenagel condensation for obtaining a series of 5-arylidene derivatives 3– 10, 13– 18. Alternatively 11, 12 and their 5-arylidene derivatives were synthesized by means of 3-phenyl-5-aryl-1-thiocarbamoyl-2-pyrazoline as S,N-binucleophile via [2 + 3]-cyclocondensation approach. The structures of compounds were determined by 1H, 13C NMR, LC–MS, EI-MS and X-ray analysis. The in vitro anticancer activity of synthesized compounds were tested by the National Cancer Institute and most of them displayed anticancer activity on leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate and breast cancer cell lines. Relations between structure and activity are discussed, the most efficient anticancer compound 16 was found to be active with selective influence on colon cancer cell lines, especially on HT 29 (log GI 50 = −6.37).

Microwave-assisted synthesis of derivatives of khellinone under phase-transfer catalytic conditions

The microwave-assisted synthesis of four new 5-acetyl-4,7-dimethoxy-6-hydroxybenzofuran (khellinone) analogs is described. The structures of the obtained derivatives in the solid state are evaluated on the basis of 13C CP/MAS NMR spectra and theoretical calculations at DFT level. A single crystal X-ray diffraction structure is presented for 8-acetyl-7-hydroxy-4-methylcoumarin. 1,4-Bis(5-acetyl-4,7-dimethoxybenzofuran-6-yloxy)butane was evaluated for potential anticancer activity in an in vitro screening panel of 60 human tumor cell lines. Selected leukemia, non-small cell lung cancer, CNS, melanoma, ovarian, and breast cancer cell lines were sensitive to this compound.

Non-nutritive functional agents in rattan-shoots, a food consumed by native people in the Philippines

The tender shoots of Calamus ornatus, one of the food items consumed by the native people, Kanawan Aytas, in the Bataan region of the Philippines, have not been studied before. A bioassay-guided investigation of its methanolic extract afforded non-nutritive functional agents (NFAs), steroidal saponins 1–3, along with its aglycone (4). The NFAs 1–4 inhibited cyclooxygenase enzymes, COX-1 and -2, by 47%, 43%, 33%, and 53% and 71%, 75%, 78%, and 73%, respectively, at 28.2, 24.2, 21.2 and 60.4μM. Treatment of breast (MCF-7), CNS (SF-268), lung (NCI-H460), colon (HCT-116) and gastric (AGS) cancer cell lines with the extract at 100μg/ml reduced cell proliferation. Similarly, the pure NFAs 2 and 3 reduced the cell viability of breast, CNS, lung, colon and gastric cancer cell lines by 37.5%, 22.4%, 53.3%, 58.2%, 40.3% and 29.8%, 21.3%, 45.6%, 37.1%, 25.0%, respectively, at 24.2 and 21.2μM. The 50% reduction in cell viability (IC50) concentrations of 2 and 3 against these cancer cell lines were 8.8, 6.1, 7.5, 23.8, 12.1 and 3.8, 7.1, 3.3, 14.3, 12.1μM, respectively. This is the first report on the isolation of steroidal saponins from C. ornatus shoots and their antiinflammatory and tumor cell proliferation inhibitory activities. Therefore, our results suggest that the Kanawan Aytas may yield health benefits from rattan-shoots in their diet.

Synthesis and antiproliferative activity of benzyl and phenethyl analogs of makaluvamines

Analogs of marine alkaloid, makaluvamine, bearing substituted benzyl and substituted phenethyl side chains have been synthesized and their antiproliferative activities have been evaluated. 4-Methyl, 4-chloro, and 4-fluoro substituted benzyl analogs possessed pronounced antiproliferative effects on the breast cancer cell line, MCF-7 at IC 50 values of 2.3 μM, 1.8 μM, and 2.8 μM, respectively. 4-Methyl, 4-chloro, and 3,4-methylenedioxy derivatives showed the best activity against MCF-7 among the phenethyl analogs with IC 50 values of 2.3 μM, 2.8 μM, and 2.4 μM, respectively. In general, methoxy substitutions resulted in slight loss in activity in both benzyl and phenethyl series. Benzyl, 4-fluorobenzyl, 3,4-dimethoxyphenethyl, and 3,4-methylenedioxyphenethyl analogs were tested by NCI in their 60 cell lines in vitro human cancer cell screen. All four compounds showed excellent inhibition against several tested cancer cell lines. Benzyl and 4-fluorobenzyl analogs were relatively more active than 3,4-dimethoxy phenethyl and 3,4-methylenedioxy phenethyl analogs. In NCI assays, the best Log GI 50 values were shown by the fluorobenzyl analog against the renal cancer cell line RXF-393 (<−8.0 M) and dimethoxy phenethyl analog against the CNS cancer cell line, SF-268 (<−8.0 M). The best Log LC 50 value was shown by the fluorobenzyl analog against the breast cancer cell line MCF-7 (−6.01 M).

Health-beneficial qualities of the edible mushroom, Agrocybe aegerita

The black poplar mushroom, Agrocybe aegerita is a popular edible mushroom with reported anti-tumor properties. A bioactivity-guided investigation gave positive results for ceramide ( 1), methyl-β- d-glucopyranoside and α- d-glucopyranoside, along with already reported linoleic acid and its methyl ester. The structure elucidation of the above was accomplished by NMR and mass spectral methods. The ceramide ( 1) inhibited cyclooxygenase enzymes, COX-1 and -2, by 43 and 92.3%, respectively at 25 μg/ml (34.4 μM). The 50% inhibition concentration (IC 50) of compound 1 against COX-2 was 5.3 μg/ml (7.3 μM). Similarly, its anti-cancer potential was investigated against five human cancer cell lines in vitro and it was found to inhibit the proliferation of stomach, breast and CNS cancer cell lines at 26.9, 23.2 and 39.1%, respectively, at 100 μg/ml (139 μM) concentration. This is the first report of the isolation of ceramide from A. aegerita and its COX and tumor cell proliferation inhibitory activities. This suggested that the consumption of A. aegerita would assist in alleviating inflammatory conditions, as well as reducing the development of the above cancers.

Effects of artemisinin and its derivatives on growth inhibition and apoptosis of oral cancer cells

Artemisinin is of special biological interest because of its outstanding antimalarial activity. Recently, it was reported that artemisinin has antitumor activity. Its derivatives, artesunate, arteether, and artemeter, also have antitumor activity against melanoma, breast, ovarian, prostate, CNS, and renal cancer cell lines. Recently, monomer, dimer, and trimer derivatives were synthesized from deoxoartemisinin, and the dimers and the trimers were found to have much more potent antitumor activity than the monomers. We evaluated the antitumor activity of artemisinin and its various derivatives (dihydroartemisinin, dihydroartemisinin 12-benzoate, 12-(2'-hydroxyethyl) deoxoartemisinin, 12-(2'-ethylthio) deoxoartemisinin dimer, deoxoartemisinin trimer) in comparison with paclitaxel (Taxol), 5-fluorouracil (5-FU), cisplatin in vitro. In this study, the deoxoartemisinin trimer had the most potent antitumor effect (IC(50) = 6.0 microM), even better than paclitaxel (IC(50) = 13.1 microM), on oral cancer cell line (YD-10B). In addition, it induced apoptosis through a caspase-3-dependent mechanism. The deoxoartemisinin trimer was found to have greater antitumor effect on tumor cells than other commonly used chemotherapeutic drugs, such as 5-FU, cisplatin, and paclitaxel. Furthermore, the ability of artemisinin and its derivatives to induce apoptosis highlights their potential as chemotherapeutic agents, for many anticancer drugs achieve their antitumor effects by inducing apoptosis in tumor cells.