Murine Leukemia P-388 Cell Line Research Articles

Synthesis, Cytotoxic Evaluation and Molecular Docking of Bromo-Substituted 1,3,6-Trihydroxyxanthone as Protein Tyrosine Kinase Inhibitor

A series of bromo-substituted hydroxyxanthone were synthesized using bromine in glacial acetic acid as a solvent, producing compounds 3 and 5 with 82.1% and 84.2% yield, respectively. In vitro analyses of these two compounds using MMT assay against murine leukemia P388 cell line resulted in IC50 of 2,550 and 3,455 μg/mL and selectivity index of 43.21 and 74.40, respectively. These results indicated that the bromo-substituted hydroxyxanthone compounds could potentially be developed as selective and sensitive anti-cancer agents. Furthermore, through the molecular docking conducted using Discovery Studio, compound 3 exhibited interactions between amino acid residues and protein tyrosine kinase (1T46.pdb). This article provides supporting data that xanthone derivatives can be used as drugs for cancer chemotherapy through the mechanism of how this compound can inhibit protein tyrosine kinase.

Total Synthesis, Stereochemical Revision, and Biological Assessment of Iriomoteolide-2a.

Iriomoteolide-2a is a marine macrolide metabolite isolated from a cultured broth of the benthic dinoflagellate Amphidinium sp. HYA024 strain. This naturally occurring substance was reported to show remarkable cytotoxic activity against human cancer cell lines HeLa and DG-75 and in vivo antitumor activity against murine leukemia P388 cell line. Herein, the total synthesis, stereochemical revision, and biological assessment of iriomoteolide-2a are reported in detail. Total synthesis of the proposed structure 1 of iriomoteolide-2a featured a late-stage convergent assembly of three components by a Suzuki-Miyaura coupling, an esterification, and a ring-closing metathesis. However, the NMR data of synthetic 1 were not identical to those of the natural product. Careful analysis of the NMR data of the authentic material and synthesis/NMR analysis of appropriately designed model compounds led to consideration of four possible stereoisomers 2-5 as candidates for the correct structure. Accordingly, total syntheses of 2-5 were achieved by taking advantage of the convergent strategy, and comparison of the NMR spectra of synthetic 2-5 with those of the natural product led to the conclusion that 5 shows the correct relative configuration of iriomoteolide-2a. The absolute configuration of this natural product was finally established through chiral HPLC analysis of synthetic 5/ent-5 with the authentic sample. The antiproliferative activity of the synthetic compounds was assessed against HeLa and A549 cells to show that, in contrast to expectation, synthetic 5 and ent-5 were only marginally active in these cell lines. This work clearly underscores the vital role of total synthesis in the establishment of the structure and biological activity of natural products.

A Flavonoid Glycoside Compound Isolated from Macaranga gigantifolia Merr Leaves

Apigenin-8-C-glycoside ( 1 ), a flavonoid glycoside compound has been isolated from the leaves of Macaranga gigantifolia Merr. Isolation and purification conducted by chromatography methods and chemical structure characterization carried out by spectroscopic methods. Cytotoxicity of Apigenin-8-C-glycoside has been tested against Murine leukemia P-388 cell lines and has moderate activity with IC 50 values 55.4 μg/mL.

Apigenin, an Anticancer Active Compound Isolated from Macaranga gigantifolia Leaves

Apigenin, a flavonoid compound has been isolated from the ethyl acetate fraction of methanol extract of Macaranga gigantifolia leaves. Isolation and purification of apigenin conducted using chromatographic method, and chemical structure characterized based on spectroscopic data. In vitro anticancer activity test against murine leukemia P-388 cell line showed potential activity with IC 50 14.13 μg/mL. Key words: apigenin, flavones, Macaranga gigantifolia , anticancer, murine leukemia P-388 cell line.

Identification and Bioactivity Studies of Flavonoid Compounds from Macaranga hispida (Blume) Mull.Arg

Two flavonoid compounds, 5,7,3’,4’-tetrahydroxy-6-geranylflavonol (1) and kaempferol 7-O-β-glucose (2) have been isolated from the leaves of Macaranga hispida (Blume) , Mull.Arg. Isolation and purification were conducted by chromatography methods and chemical structure characterization was carried out by spectroscopic methods. The 5,7,3’,4’-tetrahydrxyi-6-geranyl flavonol (1) and kaempferol 7-O-glucose (2) had moderate cytotoxic activity against murine leukemia P-388 cell lines with IC 50 value of 0.22 and 101.5 μg/mL, respectively. The IC 50 for antioxidant activities of (1) and (2) were 2.83 and 13.95 μg/mL, respectively. The LC 50 of (1) and (2) from BSLT were 350 and >1000 μg/mL, respectively.

Piceatanol: Anti-Cancer Compound From Gewang Seed Extract

Evaluation of antioxidant, antibacterial, antifungal and cytotoxic effects of Clausena suffruticosa ethanolic root extractMd. Atiar Rahman, Joti Sankhar Chakma, Saiful Islam, Nazim Uddin Ahmed

A New Flavonoid Derivative as Cytotoxic Compound Isolated from Ethyl Acetate Extract of Macaranga gigantifolia Merr. Leaves

A new prenylated flavonoid compound 5,7,3’,4’-tetrahydroxy-3,6-diprenylflavone (1) has been isolated from methanol extract of the leaves of Macaranga gigantifolia Merr. Isolation was performed using chromatography methods and their structures were elucidated based on spectroscopic data. cytotoxic activity against murine leukemia P-388 cell line conducted using MTT method. Compound 1 showed strong cytotoxic activity with IC50 value 6.19μg/mL

Murine leukemia P388 vinorelbine-resistant cell lines are sensitive to vinflunine

The work presented here was initiated to explore the mechanisms underlying vinorelbine resistance in two previously established murine leukemia P388 cell lines (N.63 and N2.5). IC(50) measurements demonstrated that the vinorelbine-resistant cell line N.63 was sensitive to both vinblastine and vinflunine. In addition, vinorelbine-resistant cell line N2.5 retained sensitivity to vinflunine. We used flow cytometry with propidium iodide to measure G2/M arrest in response to drug treatment. Annexin V labeling was used as a marker of apoptosis and JC-1 dye labeling as a marker of mitochondrial membrane depolarization to explore differential responses that might help explain the absence of cross resistance to vinflunine. At equipotent (10X IC(50)) doses, after 8 h of drug treatment, vinflunine induced G2/M arrest in a significantly larger fraction of vinorelbine- resistant cells compared to vinorelbine. At the same drug doses, at 16 h after initiation of drug treatment, vinflunine induced a statistically significant greater apoptotic response and mitochondrial depolarization. The mitochondrial depolarization at 16 h was confirmed by Western blotting that showed release of cytochrome c. Comparison of apoptotic and mitochondrial depolarization responses in vinorelbine-resistant cells upon exposure to vinorelbine, vinblastine and vinflunine demonstrated the following pattern of drug activity: vinflunine > vinblastine > vinorelbine, confirming the importance of a antimitotic-induced mitochondria-mediated pathways in these P388 cell lines. We conclude that vinflunine may be preferred for treatment of specific cancers compared to other vinca alkaloids due to its enhanced effects on apoptotic pathways that follow G2/M arrest.

Molecular diversity of Artocarpus champeden (Moraceae): A species endemic to Indonesia

A summary of results obtained in the study of natural products isolated from a Moraceae species Artocarpus champeden is presented. The various classes of 3-prenylflavonoids isolated and the biogenetical correlation between the metabolites are discussed. Some of the flavonoids exhibited strong cytotoxicity against murine leukemia P388 cell lines, suggesting that flavonoids derived from moraceous plants represent a plausible unexplored resource of novel antitumor leads.

Luotonin A. A naturally occurring human DNA topoisomerase I poison.

Luotonin A is a pyrroloquinazolinoquinoline alkaloid isolated from the Chinese herbal medicinal plant Peganum nigellastrum. Although previously shown to exhibit cytotoxicity against the murine leukemia P-388 cell line, the mechanism of action of luotonin A is unknown. Presently, we demonstrate that luotonin A stabilizes the human DNA topoisomerase I-DNA covalent binary complex, affording the same pattern of cleavage as the structurally related topoisomerase I inhibitor camptothecin. Luotonin A also mediated topoisomerase I-dependent cytotoxicity toward Saccharyomyces cerevisiae lacking yeast topoisomerase I, but harboring a plasmid having the human topoisomerase I gene under the control of a galactose promoter. This finding identifies a putative biochemical locus for the cytotoxic action of luotonin A and has important implications for the mechanism of action of camptothecin and the design of camptothecin analogues.

Chemical constituents of halophilic facultatively anaerobic bacteria, 1.

Two new nitrotyramine derivatives, 1 and 2, along with five known aromatic compounds, were isolated from the culture broth of a facultatively anaerobic, halophilic bacterium isolated from a sediment from the Great Salt Plains, Alfalfa County, Oklahoma. The structures of the new compounds were determined from spectral data and were confirmed by synthesis from tyramine hydrochloride. Compound 1 showed cytotoxicity against the murine leukemia P-388 cell line (IC50 3 micrograms/ml).

INDUCTION OF RESISTANCE TO DAUNORUBICIN IN DRUG-SENSITIVE LEUKEMIA P388 CELLS - A ROLE OF PKC-BETA-I ISOZYME

A role of protein kinase C (PKC) has been suggested in multidrug resistance (MDR). Because of the molecular and biochemical heterogeneity of PKC, we examined a role of PKC beta isozyme in drug sensitive murine leukemia P388 cell line. Drug sensitive P388 and MDR P388/ADR cells were treated with various concentrations of 12-deoxyphorbol-13-O-phenylacetate 20 acetate (DPPA, an agonist of PKC beta I isozyme) and examined for its effect on daunorubicin (DNR) accumulation and sensitivity to DNR. dPPA increased DNR resistance and decreased DNR accumulation in P388 cells but had no effect in P388/ADR cells. The reduced dPPA-induced DNR accumulation was due to decreased uptake without any effect on DNR efflux. Furthermore, treatment of P388 cells with dPPA was associated with translocation of PKC beta isozyme from cytosol to plasma membrane. These data suggest that PKC beta I isozyme plays a role in acquired drug resistance.