Antiproliferative and Antiplasmodial Dimeric Phloroglucinols from <i>Mallotus oppositifolius</i> from the Madagascar Dry Forest

Harinantenaina, Liva; Bowman, Jessica D.; Brodie, Peggy J.; Slebodnick, Carla; Callmander, Martin W.; Rakotobe, Etienne; Randrianaivo, Richard; Rasamison, Vincent E.; Gorka, Alexander P.; Roepe, Paul D.; Cassera, María B.; Kingston, David G. I.

doi:10.1021/np300750q

Cited by 40 publications

(43 citation statements)

References 33 publications

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“…Acylphloroglucinols with similar structures to compound 1 have been reported to show antibacterial activity, 18–19 and examples of phloroglucinol derivatives as antimalarial agents can be found in the literature, 20–21 but compound 1 is an order of magnitude more potent than tomentosone A, 21 the closest analog with reported antimalarial activity. Compound 1 was also tested for cytotoxicity toward human embryonic kidney cells (HEK) and no inhibition was detected up to 3.125 µM, and only 58% inhibition was observed at the highest dose tested (50 µM).…”

Section: Resultsmentioning

confidence: 97%

Antiplasmodial phloroglucinol derivatives from Syncarpia glomulifera

Dalal

Goetz

et al. 2016

Bioorganic & Medicinal Chemistry

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Bioassay guided fractionation of a MeOH extract of the stem bark of Syncarpia glomulifera (Myrtaceae) led to the isolation of the two new phloroglucinol derivatives (±)-rhodomyrtosone F (1) and (±)-calliviminone C (2), the three known triterpenes, betulinic acid (3), ursolic acid-3-acetate (4), and ursolic acid (5), and 1-(2,4,6-trihydroxyphenyl)-1-hexanone (6). Compound 1 exhibited strong antiplasmodial activity, while compounds 2 – 4 were moderately active and 5 and 6 were inactive in this assay. The structures of 1 and 2 were elucidated based on analyses of their mass spectrometric data, 1D and 2D NMR spectra, and comparison with related compounds.

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Section: Resultsmentioning

confidence: 97%

Antiplasmodial phloroglucinol derivatives from Syncarpia glomulifera

Dalal

Goetz

et al. 2016

Bioorganic & Medicinal Chemistry

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“…The D10-ACP L -GFP plasmid is maintained by 0.1 M pyrimethamine treatment (21). P. falciparum resistant to FOS was a generous gift from David Fidock (22) The effect of each compound identified as gametocytocidal was further evaluated against asexual parasites from P. falciparum strains NF54 and Dd2 using the SYBR green assay as described previously (23,24). Ten-point dilutions were used to test the dose responses at concentrations ranging from 5 M to 0.002 M. The IC 50 calculation was performed with GraFit 5 (Erithacus Software Ltd.) using nonlinear regression curve fitting and represents the average of two independent experiments and the standard deviation (SD).…”

Section: Methodsmentioning

confidence: 99%

“…FOS was used as a control drug for growth inhibition and the reversal of growth inhibition by IPP. All conditions were set in 96-well plates (200 l/well with 1% hematocrit and 1% parasitemia), incubated for 72 h, and analyzed by a SYBR green assay as described previously (23,24). The percentage of growth was normalized to that of untreated control parasites.…”

Section: Methodsmentioning

confidence: 99%

Antiapicoplast and Gametocytocidal Screening To Identify the Mechanisms of Action of Compounds within the Malaria Box

Bowman

Merino

Brooks

et al. 2014

Antimicrob Agents Chemother

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cMalaria remains a significant infectious disease that causes millions of clinical cases and >800,000 deaths per year. The Malaria Box is a collection of 400 commercially available chemical entities that have antimalarial activity. The collection contains 200 drug-like compounds, based on their oral absorption and the presence of known toxicophores, and 200 probe-like compounds, which are intended to represent a broad structural diversity. These compounds have confirmed activities against the asexual intraerythrocytic stages of Plasmodium falciparum and low cytotoxicities, but their mechanisms of action and their activities in other stages of the parasite's life cycle remain to be determined. The apicoplast is considered to be a promising source of malaria-specific targets, and its main function during intraerythrocytic stages is to provide the isoprenoid precursor isopentenyl diphosphate, which can be used for phenotype-based screens to identify compounds targeting this organelle. We screened 400 compounds from the Malaria Box using apicoplast-targeting phenotypic assays to identify their potential mechanisms of action. We identified one compound that specifically targeted the apicoplast. Further analyses indicated that the molecular target of this compound may differ from those of the current antiapicoplast drugs, such as fosmidomycin. Moreover, in our efforts to elucidate the mechanisms of action of compounds from the Malaria Box, we evaluated their activities against other stages of the life cycle of the parasite. Gametocytes are the transmission stage of the malaria parasite and are recognized as a priority target in efforts to eradicate malaria. We identified 12 compounds that were active against gametocytes with 50% inhibitory concentration values of <1 M.

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“…They exhibit various types of structural features, and various biological activities including antibacterial, antifungal, antitumor, antioxidant, antiviral, and antimalarial (5–8). Isnansetyo et al .…”

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Methicillin-resistant Staphylococcus aureus, Vancomycin-resistant Enterococcus faecalis and Enterococcus faecium active Dimeric Isobutyrylphloroglucinol from Ivesia gordonii

Ahmed

Ibrahim

Zhang

et al. 2014

Natural Product Communications

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Bioassay-guided fractionation of the chloroform soluble fraction of stem, leave, and flower extracts of the American plant Ivesia gordonii led to the isolation of a new dimeric acylphloroglucinol 3,3′-diisobutyryl-2,6′-dimethoxy-4,6,2′,4′-tetrahydroxy-5,5′dimethyldiphenyl methane (1), to which we have assigned the trivial name of ivesinol (1), together with a known monomeric acylphloroglucinol, 1,5-dihydroxy-2-(2′-methylpropionyl)-3-methoxy-6-methylbenzene (2). The structures of the isolated compounds were characterized using 1D- and 2D NMR spectroscopy, including COSY, HMQC, HMBC, and ROESY experiments as well as mass spectrometery. Ivesinol (1) showed potent activity against Staphylococcus aureus (SA) and methicillin-resistant S. aureus (MRSA) with IC50/MIC/MBC values of 0.10/1.25/>20 µg/mL and 0.05/0.31/>20 µg/mL, respectively (vs. IC50/MIC/MBC 0.133/0.5/1.0 µg/mL and 0.128/0.5/1.0 µg/mL of ciprofloxacin), while the corresponding monomer 2 was found to be less active. Compound 1 also demonstrated strong activity against vancomycin-resistant Enterococcus faecium (VRE) with IC50/MIC/MBC values 0.22/1.25/>20 µg/mL, whereas the reference standard ciprofloxacin was found to be inactive against this strain. In addition, compound 2 showed moderate activity against two species of Candida and Cryptococcus neoformans, while 1 was inactive against these fungi. In order to evaluate the influence of acyl group(s) in phloroglucinol (3) as a ligand, the mono- (4) and diacetylphloroglucinol (5) were prepared from 3, and evaluated for their in vitro SA, MRSA, and VRE activities, where 2,4-diacetylphloroglucinol (5) showed potent activity, like 1, against SA, MRSA, and VRE (ATCC 700221) with IC50/ MIC values of 0.27/2.5 µg/mL, 0.23/2.5 µg/mL, and 0.86/2.5 µg/mL, respectively, while 4 was inactive.

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Antiproliferative and Antiplasmodial Dimeric Phloroglucinols from Mallotus oppositifolius from the Madagascar Dry Forest

Cited by 40 publications

References 33 publications

Antiplasmodial phloroglucinol derivatives from Syncarpia glomulifera

Antiplasmodial phloroglucinol derivatives from Syncarpia glomulifera

Antiapicoplast and Gametocytocidal Screening To Identify the Mechanisms of Action of Compounds within the Malaria Box

Methicillin-resistant Staphylococcus aureus, Vancomycin-resistant Enterococcus faecalis and Enterococcus faecium active Dimeric Isobutyrylphloroglucinol from Ivesia gordonii

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