P388 Murine Leukemia Research Articles

Cytotoxic Steroids from The Stem Bark of Chisocheton cumingianus (Meliaceae)

Three cytotoxic steroids, stigmasterol (1), stigmast-5-en-3b-ol (2) and b-sitosterol-3-O-acetate (3) were isolated from the stem bark of Chisocheton cumingianus. The chemical structures of those compounds were identified based on spectroscopic data and by comparison with those data previously reported. All of the compounds isolated were evaluated for their cytotoxic effects against P-388 murine leukemia cells in vitro. Compounds 1-3 showed cytotoxicity activity against P-388 murine leukemia cells with IC50values of 12.4, 60.8, and ˃ 100 mg/mL, respectively.

Cytotoxic Triterpenoid from the Stembark of Chisocheton celebicus (Meliaceae)

Plants belonging to the Chisocheton genus are a rich source of tetracylic triterpenoids with diverse biological activities. Two triterpenoid compounds, dammar-20,24-dien-3-one ( 1 ) and 3β-hydroxy-tirucall-7-en ( 2 ) were isolated from the stembark of Chisocheton celebicus . The chemical structures of compounds 1 and 2 were identified by spectroscopic data, including IR, NMR ( 1 H, 13 C, DEPT 135 ° , HMQC, HMBC, 1 H- 1 H COSY), and MS, and they were compared with previously reported spectral data. Compounds 1 and 2 were evaluated for their cytotoxic effects against P-388 murine leukemia cells. The compounds showed cytotoxicity against P-388 murine leukemia cells, with IC 50 values of 30.2 and 4.3 µg/mL, respectively.

Cytotoxicity and Structure Activity Relationship of Dammarane-Type Triterpenoids from the Bark of Aglaia elliptica against P-388 Murine Leukemia Cells

Cytotoxicity and Structure Activity Relationship of Dammarane-Type Triterpenoids from the Bark of <i>Aglaia elliptica</i> against P-388 Murine Leukemia Cells

Limonoids from the Seeds of Chisocheton macrophyllus

A new limonoid compound, dysobinol (1), along with three known limonoid compounds, 7α-hydroxyneotricilenone (2), dysobinin (3), and nimonol (4), was isolated from the seeds of Chisocheton macrophyllus (Meliaceae). Their structures were established by spectroscopic techniques such as UV, IR, MS, 1D, and 2D NMR. Compounds 1–4 showed cytotoxic activity against P-388 murine leukemia cells with IC50 values of 49.7, 79.4, 19.5, and 64.5 μg/mL, respectively.

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.

Magnesium cinnamate complex, [Mg(cinn)2(H2O)2]n; structural, spectroscopic, thermal, biological and pharmacokinetical characteristics

The composition and structure of the magnesium complex with cinnamic acid, [Mg(cinn)2(H2O)2]n(1), were determined using single crystal X-ray diffraction data, IR, NMR spectroscopies, thermal and mass spectrometry analysis. Magnesium cinnamate complex, like the isostructural cobalt(II) species reported in the literature, appears to belong to the group of coordination polymers forming layered solids with pseudooctahedral coordination around the metal centre and OCO bridging units. The vibrational assignments of the experimental spectra of the complex (1) were performed on the basis of the DFT results obtained for the [Mg(cinn)4(H2O)2]2− ion, serving as a model. The complex was found to exhibit a very low cytotoxicity against neoplastic: A549 (lung), MCF-7 (breast), P388 (murine leukemia) and normal BALB3T3 (mouse fibroblasts) cell lines. In silico pharmacokinetical parameter calculations for (1) and seven known magnesium complexes with carboxylic acids: lactic, malic, glutamic, hydroaspartic and aspartic allowed for comparison of their potential bioavailability. Magnesium cinnamate complex appeared to exhibit a superior lipophilic property that suggests an optimal pharmacokinetics profile.

Flavonoid Compounds From The Leaves Of Kalanchoe Tomentosa And Their Cytotoxic Activity Against P-388 Murine Leukemia Cell

Kalanchoe plant, known as “sosor bebek” in Indonesia is a perennial herb and has succulent leaves. The plant is known in folklore and traditional medicine in Indonesia for the treatment of fever, abscesses, bruises, contused wounds, coughs and skin diseases. During the course of our continuing search for novel cytotoxic compounds, the methanolic extract of Kalanchoe tomentosa plants showed cytotoxic activity against P-388 murine leukemia cells. The methanolic extract of the fresh leaves of K. tomentosa was concentrated and extracted successively with n -hexane, ethyl acetate and n -butanol. The ethyl acetate extract exhibited strongest cytotoxic activity againts P-388 murine leukemia cells. By using the cytotoxic activity to follow the separation, the ethyl acetate fraction was separated by combination of column chromatography on silica gel and preparative TLC on silica gel GF 254 to afford a kaempferol-3- O -glycosides ( 1 ) and kaempferol-3- O -rhamnoside ( 2 ). Compound 1 and 2 showed cytotoxic activity against P-388 murine leukemia cells with IC 50 > 100μg/mL and IC 50 3.32 μg / mL

Antitumor Activity of a Polymer Composite of Etoposide and Biodegradable Poly(Lactide-Co-Glycolide)

A method for preparing an antitumor polymer form of etoposide (PFE) as submicron particles based on poly(lactide-co-glycolide) with a 50:50 ratio of monomers (PLGA 50/50) was described. It was shown that the PFE possessed high cytotoxicity against various types of human tumor cells. The activity of the PFE against multiple drug resistant K562ADR cell line was greater than that of free etoposide. A grafted solid P388 murine lymphatic leukemia model showed that the PFE exhibited high in vivo antitumor activity that was prolonged compared with that of free etoposide.

Extraction, fractionation, and chemical characterisation of fucoidans from the brown seaweed Sargassum pallidum

The fucoidans were obtained by extraction with water and gradient precipitation with different concentrations of ethanol. The main structural characterisations and bioactivities were achieved. Four fractions of water-soluble crude fucoidans with different molecular weights – SPC60, SPC70, SPH60, SPH70 – were extracted from S. pallidum collected from the Yellow Sea, China, using cold water and hot water extraction, and fractional precipitation with gradient concentrations of ethanol. Chemical analysis demonstrated that all of these fucoidan fractions consisted of fucose, rhamnose, xylose, mannose, glucose, and galactose with different monosaccharide mole ratios. Fractions SPC60, SPC70, and SPH70 showed moderate cytotoxic activity against P388 murine leukaemia cells. Fucoidan is a kind of bioactive polysaccharide from the brown algae. This study provides a fast and feasible method to obtain fucoidans from S. pallidum, which can be used as pharmaceutical material and functional food.

Synthesis and evaluation of new steroidal lactam conjugates with aniline mustards as potential antileukemic therapeutics

Alkylating agents are still nowadays one of the most important classes of cytotoxic drugs, which display a wide range of therapeutic use for the treatment of various cancers. We have synthesized and tested four hybrid homo-azasteroidal alkylating esters for antileukemic activity against five sensitive to alkylating agents human leukemia cell lines in vitro and against P388 murine leukemia in vivo. Comparatively, melphalan and 3-(4-(bis(2-chloroethyl)amino)phenoxy)propanoic acid (POPAM) were also examined. All the homo-aza-steroidal alkylators showed relatively lower acute toxicity, very promising and antileukemic activity both in vitro and in vivo.

7α-Hydroxyfriedelan-3-one-26-ol-29-oic acid and other Constituents from Pileostegia viburnoides var. glabrescens

Phytochemical investigation of the roots and rhizomes of Pileostegia viburnoides var. glabrescens led to the isolation and identification of 31 compounds (1-31), 25 of which (1-2, 4-7, 9-12, 15-18, 21-31) were isolated from the Pileostegia genus for the first time. 7α-Hydroxyfriedelan-3-one-26-ol-29-oic acid (1) is a new friedelane-type triterpene. The structure of n-butyl-β-D-fructopyranoside (2) was determined by single-crystal X-ray diffraction. Compounds 4 and 12 displayed marginal cytotoxicity against the P388 murine leukemia cell line with IC₅₀ values of 13.4 μM and 25.0 μM, respectively. Compound 23 exhibited marginal anti-inflammatory activity by the inhibition of lipopolysaccharide induced nitric oxide production in RAW 264.7 macrophage cells, with an IC₅₀ value of 32.0 μM. Compounds 3, 8-10, 25, and 27 were phytotoxic to the dicot Lactuca sativa (lettuce) and/or the monocot Agrostis stolonifera (bentgrass).

Cytototoxic constituents from the bark of Chisocheton cumingianus (Meliaceae)

A new lanostane-type triterpenoid, 3β-hydroxy-25-ethyl-lanost-9(11),24(24′)-diene (1), along with 3β-hydroxy-lanost-7-ene (2) and β-sitosterol-3-O-acetate (3) was isolated from the stem bark of C. cumingianus. The chemical structure of the new compound was elucidated on the basis of spectroscopic data. All of the compounds were evaluated for their cytotoxic effects against P-388 murine leukemia cells. Compounds 1-3 showed cytotoxicity against P-388 murine leukemia cells with IC50 values of 28.8 ± 0.10, 4.29 ± 0.03, and 100.18 ± 0.16 μg/ml, respectively.

Pterocellin A isolated from marine bryozoan Pterocella vesiculosa is cytotoxic to human HeLa cells via mitochondrial apoptotic processes.

Pterocellin A is a novel bioactive alkaloid isolated from the New Zealand marine bryozoan Pterocella vesiculosa. It exhibits potent antitumour activity towards the P388 (murine leukaemia) cell line in vitro and is selectively sensitive towards certain non-small cell lung, melanoma, and breast cancer cell lines, however, the biological mode of action of pterocellin A is unknown. Using the human cervical cancer cell line HeLa, we show that pterocellin A exhibited cytotoxicity against HeLa cells with an IC50 of 886 ng/mL. Time-course MTT and LDH assays were carried out and the results showed only a low level of cytosolic LDH was detected in the supernatant after all the cells have died from pterocellin A treatment at 2000 ng/mL. This indicated the cells maintained membrane integrity upon cell death which suggested apoptotic cell death. Additionally, morphological changes were observed under the microscope after 6 h of treatment. Cell shrinkage and nucleus condensation were observed, as well as apparent membrane blebbing, a key feature of apoptosis. The MTT data was also indicative of mitochondria impairment which could suggest that pterocellin A targets the mitochondria. This idea was supported by the observed changes in the morphology and location of the mitochondria after exposure to pterocellin A. Furthermore, the level of activated caspase-3 in HeLa cells increased after treatment with pterocellin A; activated caspase-3 can only be detected after a series of signalling events following the induction of apoptosis. These data support the notion that pterocellin A is an inducer of apoptosis in HeLa cells possibly via mitochondria related processes.

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.

Synthesis, structure and cytotoxic activity of acetylenic derivatives of betulonic and betulinic acids

A series of acetylenic derivatives of betulonic and betulinic acids has been synthesized and characterized by 1H and 13C NMR, IR and MS spectroscopy. The structure of propargyl betulonate 4 and propargyl betulinate-DMF solvate 8A was solved by X-ray diffraction. Thermal properties were examined using a DSC technique. The resulting alkynyl derivatives, as well as betulin 1 and betulinic acid 3, were evaluated in vitro for their cytotoxic activity against human T47D breast cancer, CCRF/CEM leukemia, SW707 colorectal, murine P388 leukemia and BALB3T3 normal fibroblasts cell lines. Several of the obtained compounds have a favorable cytotoxic profile than betulin 1. Propargyl betulinate 8 was the most active derivative, being up to 3-fold more potent than betulin 1 against the human leukemia (CCRF/CEM) cell line, with an IC50 value of 3.9 μg/mL.

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.

New bisamide compounds from the bark of Aglaia eximia (Meliaceae)

Two new bisamide compounds, eximiamide A (1) and eximiamide B (2) were isolated from the bark of Aglaia eximia (Meliaceae). The chemical structures of the new compound were elucidated on the basis of spectroscopic data. All of the compounds were evaluated for their cytotoxic effects against P-388 murine leukemia cells. Compounds 1 and 2 exhibited cytotoxic activity against P-388 murine leukemia cells with IC50 values of 7.6 and 8.5μg/mL, respectively.

PEMISAHAN SENYAWA-SENYAWA YANG BERSIFAT SITOTOKSIK TERHADAP SEL MURIN LEUKEMIA P388 DARI EKSTRAK METANOL KULIT BATANG DIPTEROCARPUS CONFERTUS SLOOT (DIPTEROCARPACEAE)

Six compounds, KP-1 up to KP-6 were isolated from the methanol extract of the tree bark of Dipterocarpus confertus Sloot (Dipterocarpaceae). The cytotoxic activities of these compounds were evaluated against murine leukemia P388 cells. Result of these examination indicated that KP-2 compound and KP-1 were very active with each IC 50 value of these compounds were 2.25 and 5.1 μg/mL, respectively. While the others were not active against murine leukemia P388 cells.Keywords: Dipterocarpaceae, Dipterocarpus confertus Sloot, isolated compounds, cytotoxic, and leukemia P-388 cell

Flavonoid Compounds from the Bark of Aglaia eximia (Meliaceae)

Three flavonoid compounds, kaempferol (1) , kaempferol-3- O- α-L-rhamnoside (2) , and kaempferol-3- O -β- D -glucosyl-α- L -rhamnoside (3), were isolated from the bark of Aglaia eximia (Meliaceae). The chemical structures of compounds 1–3 were identified with spectroscopic data, including UV, IR, NMR ( 1 H, 13 C, DEPT 135°, HMQC, HMBC, 1 H- 1 H-COSY NMR), and MS, as well as a compared with previously reported spectra data. All compounds were evaluated for their cytotoxic effects against P-388 murine leukemia cells. Compounds 1–3 showed cytotoxicity against P-388 murine leukemia cells with IC 50 values of 1.22, 42.92, and >100 mg/mL, respectively

In vitro 웰니스 화합물 (Ochnaflavone)에 의한 암세포 성장 저해

많은 식물들은 부작용이 적고, 가격이 저렴하며, 다양한 웰니스 융복합 화합물들을 함유하고 있기 때문에 다양한 제재에 이용되고 있다. 이 연구에서 뉴질랜드 식물인 Quintinia acutifolia (Q. acutifolia)로부터 쥐 백혈병 세포(P388 murine lymphocytic leukemia cells)의 성장을 저해하는 활성을 MTT [3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyl-tetrazolium bromide] assay에 의해 평가하였다. P388 murine lymphocytic leukemia 세포의 성장을 저해하는 2,3,2,3-tetrahydroochanaflavone (1)과 2,3-dihydroochana-flavone (3)을 1D/2D-NMR와 다른 분광학적 분석법에 의해 분리하였고, 구조를 규명하였다. 이 두 화합물은 두 개의 플라보노이드 기본구조를 갖는 바이플라보노이드 (biflavonoid)로써 2,3,2,3-Tetrahydroochnaflavone (1)과 2,3-dihydroochana-flavone (3) 화합물은 P388 murine lymphocytic leukemia세포에 대해 50%의 성장저해를 나타내는 농도가 각각 $8.2{\mu}g/mL$ 와 $3.1{\mu}g/mL$ 로 나타났다. 특히 2,3-dihydroochana-flavone (3) 화합물은 2,3,2,3-tetrahydroochanaflavone (1)의 B 링(ring)에 쌍으로 결합되지 않은 플라본 구조 (unconjugated flavonone system)를 갖는 것으로 나타났다. 그럼으로 두 화합물은 향후 항암 치료제 개발에 이용될 수 있으며, 더 많은 연구가 요구된다. 【Medicinal plants containing wellness-fusion-complex compound are increasingly being pursued as suitable alternative sources of various biological properties. In this study, inhibitory effect of Quintinia acutifolia, which is a New Zealand plant, on P388 murine lymphocytic leukemia cells using MTT [3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyl-tetrazolium bromide] assay. Based on $^1H-NMR$ , $^{13}C-NMR$ spectral data and other spectral analysis, 2,3,2,3-tetrahydroochanaflavone (1) and 2,3-dihydroochana-flavone (3) inhibited the leukemia cells were purified from the plants. 2,3,2,3-tetrahydroochanaflavone (1) and 2,3-dihydroochana-flavone (3) are biflavonoids possessing two basic flavonoids and actively inhibited growth of P388 murine lymphocytic leukemia cells with a 50% inhibitory concentration ( $IC_{50}$ ) of $8.2{\mu}g/mL$ and $3.1{\mu}g/mL$ , respectively. Specially, 2,3-dihydroochana-flavone (3) possessed unconjugated flavonone system, which isn't consist of a pair with B ring of 2,3,2,3-tetrahydroochanaflavone (1). Therefore, the two compounds could be considered as a candidate for development of anticancer drugs and need to much studies in the future.】