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Antibacterial and Cytotoxic Activity of Compounds Isolated from Flourensia oolepis.

ABSTRACT: The antibacterial and cytotoxic effects of metabolites isolated from an antibacterial extract of Flourensia oolepis were evaluated. Bioguided fractionation led to five flavonoids, identified as 2',4'-dihydroxychalcone (1), isoliquiritigenin (2), pinocembrin (3), 7-hydroxyflavanone (4), and 7,4'-dihydroxy-3'-methoxyflavanone (5). Compound 1 showed the highest antibacterial effect, with minimum inhibitory concentration (MIC) values ranging from 31 to 62 and 62 to 250??g/mL, against Gram-positive and Gram-negative bacteria, respectively. On further assays, the cytotoxic effect of compounds 1-5 was determined by MTT assay on acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML) cell lines including their multidrug resistant (MDR) phenotypes. Compound 1 induced a remarkable cytotoxic activity toward ALL cells (IC50 = 6.6-9.9??M) and a lower effect against CML cells (IC50 = 27.5-30.0??M). Flow cytometry was used to analyze cell cycle distribution and cell death by PI-labeled cells and by Annexin V/PI staining, respectively. Upon treatment, 1 induced cell cycle arrest in the G2/M phase accompanied by a strong induction of apoptosis. These results describe for the first time the antibacterial metabolites of F. oolepis extract, with 1 being the most effective. This chalcone also emerges as a selective cytotoxic agent against sensitive and resistant leukemic cells, highlighting its potential as a lead compound.

SUBMITTER: Joray MB

PROVIDER: S-EPMC4706877 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Antibacterial and Cytotoxic Activity of Compounds Isolated from Flourensia oolepis.

Joray Mariana Belén MB Trucco Lucas Daniel LD González María Laura ML Napal Georgina Natalia Díaz GN Palacios Sara María SM Bocco José Luis JL Carpinella María Cecilia MC

Evidence-based complementary and alternative medicine : eCAM 20151227

The antibacterial and cytotoxic effects of metabolites isolated from an antibacterial extract of Flourensia oolepis were evaluated. Bioguided fractionation led to five flavonoids, identified as 2',4'-dihydroxychalcone (1), isoliquiritigenin (2), pinocembrin (3), 7-hydroxyflavanone (4), and 7,4'-dihydroxy-3'-methoxyflavanone (5). Compound 1 showed the highest antibacterial effect, with minimum inhibitory concentration (MIC) values ranging from 31 to 62 and 62 to 250 μg/mL, against Gram-positive a ...[more]

PMID: 26819623

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Project description:Natural products remain a viable source of novel therapeutics, and as detection and extraction techniques improve, we can identify more molecules from a broader set of plant tissues. The aim of this study was an investigation of the cytotoxic and anti-plasmodial activities of the methanol extract from Stephania dielsiana Y.C. Wu leaves and its isolated compounds. Our study led to the isolation of seven alkaloids, among which oxostephanine (1) is the most active against several cancer cell lines including HeLa, MDA-MB231, MDA-MB-468, MCF-7, and non-cancer cell lines, such as 184B5 and MCF10A, with IC50 values ranging from 1.66 to 4.35 μM. Morever, oxostephanine (1) is on average two-fold more active against cancer cells than stephanine (3), having a similar chemical structure. Cells treated with oxostephanine (1) are arrested at G2/M cell cycle, followed by the formation of aneuploidy and apoptotic cell death. The G2/M arrest appears to be due, at least in part, to the inactivation of Aurora kinases, which is implicated in the onset and progression of many forms of human cancer. An in-silico molecular modeling study suggests that oxostephanine (1) binds to the ATP binding pocket of Aurora kinases to inactivate their activities. Unlike oxostephanine (1), thailandine (2) is highly effective against only the triple-negative MDA-MB-468 breast cancer cells. However, it showed excellent selectivity against the cancer cell line when compared to its effects on non-cancer cells. Furthermore, thailandine (2) showed excellent anti-plasmodial activity against both chloroquine-susceptible 3D7 and chloroquine-resistant W2 Plasmodium falciparum strains. The structure-activity relationship of isolated compound was also discussed in this study. The results of this study support the traditional use of Stephania dielsiana Y.C. Wu and the lead molecules identified can be further optimized for the development of highly effective and safe anti-cancer and anti-plasmodial drugs.

Project description:BackgroundAngelica shikokiana is a Japanese medicinal herb that is included among food and drug preparations protecting against cancer; however, there is no previous report about the cytotoxicity of A. shikokiana or its bioactive compounds.ObjectiveThis study was designed to investigate the cytotoxic activities of A. shikokiana methanol extract (AME) and its isolated compounds and to identify the molecular mechanisms of the cytotoxicity.Materials and methodsCytotoxicity and selectivity was investigated by measuring the IC50 values on five cancer cell lines; human hepatocellular carcinoma, rhabdomyosarcoma (RD), colorectal carcinoma, human epithelioma and human breast adenocarcinoma and one normal cell line; human lung fibroblasts. The effects on tubulin polymerization and histone deacetylase 8 (HDAC8), were examined to determine the mechanism of cytotoxicity. Docking study was designed to examine the binding affinity to the target molecules.ResultsMethanol extract and some of its isolated coumarins and flavonoids showed potent, selective cytotoxicity against cancer cell lines. AME and all isolated compounds inhibited tubulin polymerization. Angelicin and kaempferol-3-O-rutinoside were the most active compounds. Phenolic compounds and furanocoumarins showed binding affinity to colchicine binding site rather than the vinblastine binding site of tubulin microtubules. On the other side, quercetin, kaempferol, luteolin, chlorogenic acid, and methyl chlorogenate exhibited the strongest activity against HDAC8 and the highest affinity to trichostatin A binding site.ConclusionThese findings provide the first scientific evidence of the cytotoxicity of AME through inhibition of tubulin polymerization and HDAC8 activity through its coumarin and flavonoid content.SummaryThe present study provides for the first time a clue for the cytotoxic activities of the AME. Our results indicate that the cytotoxic activities are partially related to the ability of AME to inhibit tubulin polymerization and HDAC8 activity. Isolated compounds; Angelicin and kaempferol-3-O-rutinoside showed the strongest inhibition of tubulin polymerization through binding to colchicine binding domain of tubulin microtubules. Phenolic compounds; quercetin, luteolin, kaempferol, chlorogenic acid and methyl chlorogenate exhibited a strong inhibition of HDAC8 through binding to TSA binding site. This, however, further detailed pharmacological and in vivo studies should be the next step in evaluating the cytotoxic activities of AME and its active compounds that are currently ongoing. Abbreviations used: AME: Methanol extract of the aerial part of A. shikokiana, HDACs: Histone deacetylases,HDAC8: Histone deacetylase 8.

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Antibacterial and Cytotoxic Activity of Compounds Isolated from Flourensia oolepis.

Publications

Antibacterial and Cytotoxic Activity of Compounds Isolated from Flourensia oolepis.

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