@article{rojas-silva_graziose_vesely_poulev_mbeunkui_grace_kyle_lila_raskin_2014, title={Leishmanicidal activity of a daucane sesquiterpene isolated from Eryngium foetidum}, volume={52}, ISSN={["1744-5116"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84893248952&partnerID=MN8TOARS}, DOI={10.3109/13880209.2013.837077}, abstractNote={Abstract Context: Eryngium foetidum L. (Apiaceae) is a traditional herb that has been used for numerous medicinal applications, including as a treatment for parasitic infections, especially in the Neotropics from where it originates. Objective: This study evaluates the in vitro leishmanicidal and cytotoxicity activities of isolated compounds based on a bioassay-guided fractionation approach. Materials and methods: Defatted aerial parts of E. foetidum were subjected to extraction with methanol followed by partitioning with n-hexane, ethyl acetate and 50% methanol. Then, the first two fractions were subsequently fractionated by column chromatography and HPLC. Compound identity was confirmed by mass spectrometry and NMR spectroscopy. Leishmania tarentolae (promastigotes) and L. donovani (amastigotes) were used as testing parasites. L6 rat myoblasts were used for cytotoxicity. All extracts and fractions were tested at 20 μg/mL. Results: The initial methanol extract showed 20% growth inhibition of L. tarentolae. Then, the n-hexane and ethyl acetate fractions were also active showing approximately 40% growth inhibition. From these two fractions, the following compounds were isolated: lasidiol p-methoxybenzoate (1), a daucane sesquiterpene; and 4-hydroxy-1,1,5-trimethyl-2-formyl-cyclohexadien-(2,5)-[α-acetoxymethyl-cis-crotonate] (2), a terpene aldehyde ester derivative. Compound 1 inhibited the growth of both L. tarentolae and L. donovani with IC50 values of 14.33 and 7.84 μM, respectively; and showed no cytotoxicity (IC50 > 50 μM). Compound 2 was inactive in the L. tarentolae assay (IC50 > 50 μM). Discussion and conclusion: This study presented the bioassay-guided fractionation with the leishmanicidal and cytotoxicity activities of two compounds isolated for the first time from an Eryngium species.}, number={3}, journal={PHARMACEUTICAL BIOLOGY}, author={Rojas-Silva, Patricio and Graziose, Rocky and Vesely, Brian and Poulev, Alexander and Mbeunkui, Flaubert and Grace, Mary H. and Kyle, Dennis E. and Lila, Mary Ann and Raskin, Ilya}, year={2014}, month={Mar}, pages={398–401} }
 @article{yousef_brown_funakoshi_mbeunkui_grace_ballington_loraine_lila_2013, title={Efficient Quantification of the Health-Relevant Anthocyanin and Phenolic Acid Profiles in Commercial Cultivars and Breeding Selections of Blueberries (Vaccinium spp.)}, volume={61}, ISSN={["1520-5118"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84878264623&partnerID=MN8TOARS}, DOI={10.1021/jf400823s}, abstractNote={Anthocyanins and phenolic acids are major secondary metabolites in blueberry with important implications for human health maintenance. An improved protocol was developed for the accurate, efficient, and rapid comparative screening for large blueberry sample sets. Triplicates of six commercial cultivars and four breeding selections were analyzed using the new method. The compound recoveries ranged from 94.2 to 97.5 ± 5.3% when samples were spiked with commercial standards prior to extraction. Eighteen anthocyanins and 4 phenolic acids were quantified in frozen and freeze-dried fruits. Large variations for individual and total anthocyanins, ranging from 201.4 to 402.8 mg/100 g, were assayed in frozen fruits. The total phenolic acid content ranged from 23.6 to 61.7 mg/100 g in frozen fruits. Across all genotypes, freeze-drying resulted in minor reductions in anthocyanin concentration (3.9%) compared to anthocyanins in frozen fruits. However, phenolic acids increased by an average of 1.9-fold (±0.3) in the freeze-dried fruit. Different genotypes frequently had comparable overall levels of total anthocyanins and phenolic acids, but differed dramatically in individual profiles of compounds. Three of the genotypes contained markedly higher concentrations of delphinidin 3-O-glucoside, cyanidin 3-O-glucoside, and malvidin 3-O-glucoside, which have previously been implicated as bioactive principles in this fruit. The implications of these findings for human health benefits are discussed.}, number={20}, journal={JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY}, author={Yousef, Gad G. and Brown, Allan F. and Funakoshi, Yayoi and Mbeunkui, Flaubert and Grace, Mary H. and Ballington, James R. and Loraine, Ann and Lila, Mary A.}, year={2013}, month={May}, pages={4806–4815} }
 @article{grace_massey_mbeunkui_yousef_lila_2012, title={Comparison of Health-Relevant Flavonoids in Commonly Consumed Cranberry Products}, volume={77}, ISSN={["1750-3841"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84864624023&partnerID=MN8TOARS}, DOI={10.1111/j.1750-3841.2012.02788.x}, abstractNote={Abstract:  The human health benefits from consumption of cranberry products have been associated with the fruits’ unique flavonoid composition, including a complex profile of anthocyanins and proanthocyanidins. However, when processed by techniques such as pressing, canning, concentrating, or drying, a number of these natural components may be compromised or inactivated due to physical separation, thermal degradation, or oxidation. Fresh cranberries were compared to freeze‐dried berries and individual fruit tissues (skin and peeled fruit). Products examined included cranberry juices (commercial and prepared from concentrate), cranberry sauces (commercial and homemade), and sweetened‐dried cranberries (commercial). Freeze‐drying resulted in no detectable losses of anthocyanins or proanthocyanidins from cranberry fruits. Anthocyanins were localized in the skin. Proanthocyanins were higher in the skin than in the flesh, with the exception of procyanidin A‐2 dimer which was concentrated in the flesh. Anthocyanins were significantly higher in not‐from‐concentrate juice than in reconstituted juice from concentrate (8.3 mg and 4.2 mg/100 mL, respectively). Similarly, proanthocyanidins were markedly higher in not‐from‐concentrate juice compared to juice from concentrate (23.0 mg and 8.9 mg/100 mL, respectively). Homemade sauce contained far higher anthocyanins and proanthocyanidins (15.9 and 87.9 mg/100 g, respectively) than canned sauces processed with whole berries (9.6 and 54.4 mg/100 g, respectively) or jelled‐type (1.1 and 16 mg/100 g, respectively). Sweetened‐dried cranberries were quite low in anthocyanins (7.9 mg/100 g), but they still retained considerable proanthocyanidins (64.2 mg/100 g). Commercially processed products contained significantly lower levels of polyphenols as compared to fresh and home‐processed preparations. Anthocyanins were more sensitive to degradation than proanthocyanidins.}, number={8}, journal={JOURNAL OF FOOD SCIENCE}, author={Grace, Mary H. and Massey, Aaron R. and Mbeunkui, Flaubert and Yousef, Gad G. and Lila, Mary Ann}, year={2012}, month={Aug}, pages={H176–H183} }
 @article{mbeunkui_grace_lategan_smith_raskin_lila_2012, title={In vitro antiplasmodial activity of indole alkaloids from the stem bark of Geissospermum vellosii}, volume={139}, ISSN={["0378-8741"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84856012987&partnerID=MN8TOARS}, DOI={10.1016/j.jep.2011.11.036}, abstractNote={The stem bark of Geissospermum vellosii has been traditionally used by the native population of northern South America to treat malaria. Indole alkaloids have been previously isolated from this plant, but the antiplasmodial constituents have not yet been described. As part of our ongoing investigations of new bioactive compounds with activity against malaria parasites, we tested the in vitro antiplasmodial activity of isolated fractions and purified alkaloids from Geissospermum vellosii.Indole alkaloids were isolated and identified from a methanolic crude extract of Geissospermum vellosii bark using a combination of high performance counter current chromatography, mass spectrometry and nuclear magnetic resonance technologies. The methanolic extract, the crude alkaloid fractions and the purified compounds were tested for in vitro antiplasmodial activity against the chloroquine-sensitive strain of Plasmodium falciparum (D10).An indole alkaloid (4) along with four known indole alkaloids, geissolosimine (1), geissospermine (2), geissoschizoline (3), and vellosiminol (5) were isolated and structure elucidated. The antiplasmodial activity (IC(50)) of the methanolic crude extract was 2.22 μg/mL, while for the isolated compounds it ranged from 0.96 μM to 13.96 μM except for (5) which showed a low activity (157 μM). Geissolosimine (1) showed the highest antiplasmodial activity (0.96 μM).This study provides evidence to support the use of Geissospermum vellosii as an antimalarial agent, as used by the native populations. Geissolosimine (1) is a lead molecular structure for possible antimalarial drug development.}, number={2}, journal={JOURNAL OF ETHNOPHARMACOLOGY}, author={Mbeunkui, Flaubert and Grace, Mary H. and Lategan, Carmen and Smith, Peter J. and Raskin, Ilya and Lila, Mary Ann}, year={2012}, month={Jan}, pages={471–477} }
 @article{mbeunkui_grace_yousef_lila_2012, title={Isolation and characterization of flavonols from blackcurrant by high-performance counter-current chromatography and electrospray ionization tandem mass spectrometry}, volume={35}, ISSN={["1615-9314"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84863684478&partnerID=MN8TOARS}, DOI={10.1002/jssc.201200198}, abstractNote={Blackcurrant is considered as a natural high‐value food raw material and possesses a variety of therapeutic properties. The health benefits of blackcurrant have generally been credited to its high anthocyanin content; however, the therapeutic properties of other minor flavonoids constituents have not yet been investigated due the difficulties related to their isolation. Multiple steps of high‐performance counter‐current chromatography in combination with ESI tandem mass spectrometry (MSn) were successfully used for the preparative isolation of flavonols from blackcurrant extract, to study their electrospray ionization mass spectrometry fragmentation behavior. Seven flavonols, namely myricetin‐3‐O‐rutinoside (145.5 mg), myricetin‐3‐O‐hexoside (79.7 mg), myricetin‐3‐O‐(6″‐malonyl)‐glucoside (17.4 mg), kaempferol‐3‐O‐glucoside (20.5 mg), quercetin‐3‐O‐rutinoside (55.1 mg), quercetin‐3‐O‐hexoside (25.8 mg), and myricetin (129.1 mg) have been successfully isolated and their multistage MSn data were used for detailed structure characterization. The results of these experiments demonstrated that high‐performance counter‐current chromatography along with ESI‐MSn is a sensitive, selective, and effective technology for isolation and characterization of minor constituents from a complex mixture.}, number={13}, journal={JOURNAL OF SEPARATION SCIENCE}, author={Mbeunkui, Flaubert and Grace, Mary H. and Yousef, Gad G. and Lila, Mary Ann}, year={2012}, month={Jul}, pages={1682–1689} }
 @article{mbeunkui_grace_lila_2012, title={Isolation and structural elucidation of indole alkaloids from Geissospermum vellosii by mass spectrometry}, volume={885}, journal={Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences}, author={Mbeunkui, F. and Grace, M. H. and Lila, M. A.}, year={2012}, pages={83–89} }
 @inproceedings{rojas-silva_graziose_poulev_mbeunkui_grace_lila_raskin_2012, title={Seeking novel Leishmanicidal natural products from common medicinal plants, the example of Eryngium foetidum L}, volume={78}, number={11}, booktitle={Planta Medica}, author={Rojas-Silva, P. and Graziose, R. and Poulev, A. and Mbeunkui, F. and Grace, M. H. and Lila, M. A. and Raskin, I.}, year={2012}, pages={1132–1132} }
 @article{mbeunkui_goshe_2011, title={Investigation of solubilization and digestion methods for microsomal membrane proteome analysis using data-independent LC-MSE}, volume={11}, ISSN={["1615-9861"]}, DOI={10.1002/pmic.200900698}, abstractNote={Abstract}, number={5}, journal={PROTEOMICS}, author={Mbeunkui, Flaubert and Goshe, Michael B.}, year={2011}, month={Mar}, pages={898–911} }
 @article{mbeunkui_grace_lategan_smith_raskin_lila_2011, title={Isolation and identification of antiplasmodial N-alkylamides from Spilanthes acmella flowers using centrifugal partition chromatography and ESI-IT-TOF-MS}, volume={879}, ISSN={1570-0232}, url={http://dx.doi.org/10.1016/j.jchromb.2011.05.013}, DOI={10.1016/j.jchromb.2011.05.013}, abstractNote={The development of new antiplasmodial drugs is of primary importance due to the growing problem of multi-drug resistance of malaria parasites. Spilanthes acmella, a plant traditionally used for the treatment of toothache, was targeted as a lead for its potential antiplasmodial activity. A systematic approach for investigating a suitable centrifugal partition chromatography (CPC) solvent system for N-alkylamides separation was reported. The partition behavior of three N-alkylamides has been studied using several biphasic solvent mixtures in search of an adequate CPC solvent system for this class of compounds. Major N-alkylamides in S. acmella were isolated from a methanolic crude extract of flowers by CPC with the solvent system heptanes-ethyl acetate-methanol-water (3:2:3:2, v/v/v/v). Four N-alkylamides were purified and the structures were illustrated by electrospray ionization-ion trap-time of flight-mass spectrometry (ESI-IT-TOF-MS), ¹H nuclear magnetic resonance (¹H NMR) and ¹³C nuclear magnetic resonance (¹³C NMR). The CPC fractions, which contained natural mixtures of phytochemicals, demonstrated significantly higher antiplasmodial activity compared to corresponding purified N-alkylamides, thus suggesting that interactions between these N-alkylamides may potentiate antiplasmodial bioactivity.}, number={21}, journal={Journal of Chromatography B}, publisher={Elsevier BV}, author={Mbeunkui, Flaubert and Grace, Mary H. and Lategan, Carmen and Smith, Peter J. and Raskin, Ilya and Lila, Mary Ann}, year={2011}, month={Jul}, pages={1886–1892} }
 @article{grace_lategan_mbeunkui_graziose_smith_raskin_lila_2010, title={Antiplasmodial and cytotoxic activities of drimane sesquiterpenes from Canella winterana}, volume={5}, number={12}, journal={Natural Product Communications}, author={Grace, M. H. and Lategan, C. and Mbeunkui, F. and Graziose, R. and Smith, P. J. and Raskin, I. and Lila, M. A.}, year={2010}, pages={1869–1872} }
 @article{blackburn_mbeunkui_mitra_mentzel_goshe_2010, title={Improving Protein and Proteome Coverage through Data-Independent Multiplexed Peptide Fragmentation}, volume={9}, ISSN={["1535-3907"]}, DOI={10.1021/pr100144z}, abstractNote={Performance differences in protein and proteome characterization achieved by data-independent acquisition (DIA) LC/MS(E) and data-dependent acquisition (DDA) LC/MS/MS approaches were investigated. LC/MS(E) is a novel mode of generating product ion data for all coeluting precursors in parallel as opposed to LC/MS/MS where coeluting precursors must be serially fragmented one at a time. During LC/MS(E) analysis, alternating MS scans of "normal" and "elevated" collision energy are collected at regular intervals, providing nearly a 100% duty cycle for precursor detection and fragmentation because all precursors are fragmented across their full chromatographic elution profile. This is in contrast to DDA-based MS/MS where serial selection of precursor ions is biased toward interrogation and detection of the highest abundance sample components by virtue of the intensity-driven interrogation scheme employed. Both modes of acquisition were applied to a simple four-protein standard mixture with a 16-fold dynamic range in concentration, an in-gel digest of the Arabidopsis thaliana protein FLS2 purified by immunoprecipitation, and a solution-digested tomato leaf proteome sample. Dramatic improvement for individual protein sequence coverage was obtained for all three samples analyzed by the DIA approach, particularly for the lowest abundance sample components. In many instances, precursors readily detected and identified during DIA were either interrogated by MS/MS during DDA at inopportune points in their chromatographic elution profiles resulting in poor quality product ion spectra or not interrogated at all. Detailed evaluation of both DDA and DIA raw data and timing of the MS-to-MS/MS switching events clearly revealed the fundamental limitations of serial MS/MS interrogation and the advantages of parallel fragmentation by DIA for more comprehensive protein identification and characterization which holds promise for enhanced isoform and post-translational modification analysis.}, number={7}, journal={JOURNAL OF PROTEOME RESEARCH}, author={Blackburn, Kevin and Mbeunkui, Flaubert and Mitra, Srijeet K. and Mentzel, Tobias and Goshe, Michael B.}, year={2010}, month={Jul}, pages={3621–3637} }
 @article{mbeunkui_scholl_opperman_goshe_bird_2010, title={Proteomic and Bioinformatic Analysis of the Root-Knot Nematode Meloidogyne hapla: The Basis for Plant Parasitism}, volume={9}, ISSN={1535-3893 1535-3907}, url={http://dx.doi.org/10.1021/pr1006069}, DOI={10.1021/pr1006069}, abstractNote={On the basis of the complete genome sequence of the root-knot nematode Melodogyne hapla, we have deduced and annotated the entire proteome of this plant-parasite to create a database of 14,420 proteins. We have made this database, termed HapPep3, available from the Superfamily repository of model organism proteomes (http://supfam.mrc-lmb.cam.ac.uk/SUPERFAMILY). To experimentally confirm the HapPep3 assignments using proteomics, we applied a data-independent LC/MS(E) analysis to M. hapla protein extracts fractionated by SDS-PAGE. A total of 516 nonredundant proteins were identified with an average of 9 unique peptides detected per protein. Some proteins, including examples with complex gene organization, were defined by more than 20 unique peptide matches, thus, providing experimental confirmation of computational predictions of intron/exon structures. On the basis of comparisons of the broad physicochemical properties of the experimental and computational proteomes, we conclude that the identified proteins reflect a true and unbiased sampling of HapPep3. Conversely, HapPep3 appears to broadly cover the protein space able to be experimentally sampled. To estimate the false discovery rate, we queried human, plant, and bacterial databases for matches to the LC/MS(E)-derived peptides, revealing fewer than 1% of matches, most of which were to highly conserved proteins. To provide a functional comparison of the acquired and deduced proteomes, each was subjected to higher order annotation, including comparisons of Gene Ontology, protein domains, signaling, and localization predictions, further indicating concordance, although those proteins that did deviate seem to be highly significant. Approximately 20% of the experimentally sampled proteome was predicted to be secreted, and thus potentially play a role at the host-parasite interface. We examined reference pathways to determine the extent of proteome similarity of M. hapla to that of the free-living nematode, Caenorhabditis elegans, revealing significant similarities and differences. Collectively, the analyzed protein set provides an initial foundation to experimentally dissect the basis of plant parasitism by M. hapla.}, number={10}, journal={Journal of Proteome Research}, publisher={American Chemical Society (ACS)}, author={Mbeunkui, Flaubert and Scholl, Elizabeth H. and Opperman, Charles H. and Goshe, Michael B. and Bird, David McK.}, year={2010}, month={Oct}, pages={5370–5381} }
 @misc{mbeunkui_johann_2009, title={Cancer and the tumor microenvironment: A review of an essential relationship}, volume={63}, number={4}, journal={Cancer Chemotherapy and Pharmacology}, author={Mbeunkui, F. and Johann, D. J.}, year={2009}, pages={571–582} }