Renato Murillo

University of Costa Rica, San José, San José, Costa Rica

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Publications (28)77.14 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The leaves of Zuelania guidonia yielded eight new clerodane diterpenes, namely, zuelaguidins A-H (1-8), and the known clerodane diterpene esculentin A (9). Some of these structures contained a 3,6-dihydro-1,2-dioxin moiety. The new compounds were isolated and identified using 1D- and 2D-NMR experiments. All compounds were evaluated for cytotoxicity against the CCRF-CEM (human acute lymphocytic leukemia), CEM-ADR5000 (human acute lymphocytic leukemia resistant to doxorubicin), and MIA-PaCa-2 (human pancreatic carcinoma) cell lines as well as for their selectivity against peripheral blood mononuclear cells from healthy human subjects. Zuelaguidins B, C, and E were the most potent compounds against the CCRF-CEM cell line, with IC50 values ranging from 1.6 to 2.5 μM.
    Journal of Natural Products 01/2014; · 3.29 Impact Factor
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    ABSTRACT: Four new flavonol glycosides were isolated from the leaves of Brugmansia suaveolens: kaempferol 3-O-β-D-glucopyranosyl-(1'''→2'')-O-α-L-arabinopyranoside (1), kaempferol 3-O-β-D-glucopyranosyl-(1'''→2'')-O-α-L-arabinopyranoside-7-O-į-D-gluco-pyranoside (2), kaempferol 3-O-β-D-[6'''-O-(E-caffeoyl)]-glucopyranosyl-(1'''→2'')-O-α-l-arabinopyranoside-7-O-β-D-glucopyranoside (3), and kaempferol 3-O-β-D-[2'''-O-(E-caffeoyl)]-glucopyranosyl-(1'''→2'')-O-α-l-arabinopyranoside-7-O-β-D-glucopyranoside (4). The structure elucidation was performed by MS, 1D and 2D NMR analyses.
    Planta Medica 01/2014; 19(5):6727-6736. · 2.35 Impact Factor
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    ABSTRACT: Following our phytochemical studies of Costa Rican plants, we report the isolation of two new 3,4-seco-ent-kaurenes from the aerial parts of Croton megistocarpus (Euphorbiaceae). The structures of the two compounds were elucidated as 14-[(2-methylbutanoyl)oxy]-3,4-seco-ent-kaura-4(19),16-dien-3-oic acid (1) and 14-{[(2Z)-2-methylbut-2-enoyl]oxy}-3,4-seco-ent-kaura-4(19),16-dien-3-oic acid (2). In addition, seven known diterpene clerodanes were also isolated and identified. The structures of the compounds were elucidated by spectroscopic methods, including HR-MS, 1H-NMR, 13C-NMR, COSY, HMQC, HMBC, and NOESY experiments.
    Helvetica Chimica Acta 10/2011; 94(10). · 1.38 Impact Factor
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    ABSTRACT: Phytochemical investigations of the n-hexane extract from the roots of Peltodon longipes (Lamiaceae) resulted in the isolation of 12 known abietane diterpenes (1-12). Structures were established on the basis of one and two dimensional nuclear magnetic resonance spectroscopic data ((1)H and (13)C, COSY, HSQC and HMBC), electron ionization mass spectrometric analysis (EIMS) as well as comparison with data from literature. These compounds, as well as eight known diterpenes (13-19) from Salvia miltiorrhiza, and two from Salvia sahendica (20 and 21) were evaluated for their cytotoxic effects in human pancreatic (MIAPaCa-2) and melanoma (MV-3) tumor cell lines using the MTT assay. Tanshinone IIa (13), 7α-acetoxyroyleanone (1), 1,2-dihydrotanshinone (16) and cryptotanshinone (14) had the highest cytotoxic effects in MIAPaCa-2, displaying IC(50) of 1.9, 4.7, 5.6, and 5.8 μM, respectively. Structure-activity relationships of abietane diterpenoid quinones are discussed.
    Bioorganic & medicinal chemistry 08/2011; 19(16):4876-81. · 2.82 Impact Factor
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    ABSTRACT: Structure elucidation and conformation analysis of four proanthocyanidins isolated from the bark of Parapiptadenia rigida were performed by two-dimensional NMR spectroscopy, HRESIMS, CD, and molecular mechanics (MM+) force field calculations. The known prodelphinidin, epigallocatechin-(4β→8)-epigallocatechin-3-O-gallate (1) was accompanied by the new epigallocatechin-(4β→8)-4'-O-methylgallocatechin (2), epicatechin-(4β→8)-4'-O-methylgallocatechin (3), and (4α→8)-bis-4'-O-methylgallocatechin (4). Compound 4 was previously published but the earlier structure must presumably be revised to 4'-O-methylgallocatechin-(4α→8)-4'-O-methylepigallocatechin. Conformational studies showed the compact rotamer with B and E rings in quasi-equatorial orientations as the preferred conformation for compounds 1-3, whereas 4 consists of two stable rotamers, each with a quasi-equatorial orientation of ring B and E, respectively. The isolated compounds were studied for their wound-healing effects in a scratch assay and showed promising results.
    Journal of Natural Products 06/2011; 74(6):1427-36. · 3.29 Impact Factor
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    ABSTRACT: Analysis of the ethanolic extract of the bark from Parapiptadenia rigida resulted in the isolation of the new catechin derivatives 4',3''-di-O-methylapocynin-D (10), 4',3''-di-O-methylapocynin-B (11), epigallocatechin-3-O-ferulate (8), and 4'-O-methylepigallocatechin-3-O-ferulate (9) and the catechins 4'-O-methylepigallocatechin-3-O-gallate (6) and 4'-O-methylepicatechin-3-O-gallate (7). These compounds, isolated for the first time from a natural source, are accompanied by the five known catechins 4'-O-methylgallocatechin (1), 4'-O-methylepigallocatechin (2), 3'-O-methylepicatechin (3), epigallocatechin-3-O-gallate (4), and epicatechin-3-O-gallate (5). Compounds 5 and 7 displayed promising wound-healing effects in a scratch assay. Some of the catechin derivatives showed inhibitory effects on NF-κB DNA binding and p38α MAPK activity.
    Journal of Natural Products 11/2010; 73(12):2035-41. · 3.29 Impact Factor
  • Planta Medica 08/2010; 76(12). · 2.35 Impact Factor
  • Planta Medica - PLANTA MED. 01/2010; 76(12).
  • Revista de biologia tropical 09/2008; 56(3):1043-1051. · 0.55 Impact Factor
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    ABSTRACT: Sesquiterpene lactones are the active components of a variety of medicinal plants from the Asteraceae family. They possess biological activities such as the inhibition of NF-kappaB and the release inhibition of the vasoactive serotonin. On the basis of a data set of 54 SLs, we report the development of a quantitative model for the prediction of serotonin release inhibition. Comparing this model with a previous investigation of the target NF-kappaB, structural features necessary for specific compounds could be acquired. Atomic properties encoded by radial distribution function and molecular surface potentials encoded by autocorrelation were used as descriptors. Whereas some descriptors describe the structural requirements for both activities, other descriptors can be used to decide whether an SL is more active to NF-kappaB or to serotonin release. Again, counter propagation neural networks proved to be a valuable tool to establish structure-activity relationships that are necessary for the search for and optimization of lead structures.
    Journal of Medicinal Chemistry 04/2008; 51(5):1324-32. · 5.61 Impact Factor
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    ABSTRACT: Sesquiterpene lactones (SQTLs) are shown to possess anti-inflammatory as well as cytotoxic activity. No study, however, links both activities. We, therefore, hypothesized that SQTL-treated, dying cells might induce an anti-inflammatory response in cocultured THP-1 macrophages. Here we show that SQTLs bearing either an alpha,beta-unsaturated cyclopentenone or an alpha-methylene-gamma-lactone induce different forms of cell death. Whereas the cyclopentenone SQTL induced typical apoptosis, the alpha-methylene-gamma-lactone SQTLs-induced cell death lacked partly classical signs of apoptosis, such as DNA fragmentation. All SQTLs, however, activated caspases and the nuclear morphology of cell death was dependent on caspase activation. Most interestingly, alpha-methylene-gamma-lactone SQTLs induced a more pronounced phosphatidylserine (PS) exposure than the cyclopentenone SQTL. Especially, 7-hydroxycostunolide (HC), with an alpha-methylene-gamma-lactone substituted with a hydroxyl group, showed a striking fast and pronounced PS translocation. This result was in agreement with a strong activation of phagocytosis in cocultured THP-1 macrophages. Interestingly, HC-treated Jurkat cells led to an early (3.5 h) but transient increase in TNF-alpha levels in macrophage coculture. Release of TGF-beta remained unaffected after 18 h. We propose that this type of SQTL may influence local inflammation by transiently activating the immune system and help to clear cells by inducing a form of cell death that promotes phagocytosis.
    APOPTOSIS 02/2007; 12(1):141-53. · 3.95 Impact Factor
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    Ciencia y Tecnologia. 12/2006; 24(217-226).
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    ABSTRACT: Twenty-four structurally different SLs were studied for their inhibition on IL-8 production in HeLa229 cells and different IC50-values were obtained. QSAR analyses revealed that the alpha-methylene-gamma-lactone and the presence and reactivity of a second reaction center, expressed by LUMO2, are the most important descriptors for IL-8. Using two SLs as examples, we demonstrated that SLs prevent DNA binding of AP-1, which has binding sites in the IL-8 promoter together with NF-kappaB and C/EBP, and that this is probably due to directly targeting AP-1. p38 MAPK, which plays a role in AP-1 activation as well as in IL-8 regulation, was not influenced by SLs. These data show that NF-kappaB and AP-1, and consequently IL-8 may be interesting targets in antiinflammation research and that the small molecules of SLs may be powerful candidates with promising properties for therapeutic modulation of the inflammatory response.
    Bioorganic & Medicinal Chemistry 05/2006; 14(8):2487-97. · 2.90 Impact Factor
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    ABSTRACT: Investigation of the aerial parts of Vernonia triflosculosa afforded three hirsutinolides of which 8alpha-(4alpha-hydroxymethacryloyloxy)-10alpha-hydroxy-1,13-dimethoxy-hirsutinolide is new, three ent-kaurane diterpenes, among which the 19-[alpha-L-arabinopyranosyl-(1-->2)-beta-D-glucopyranosyl] esters of 16beta-hydroxy-ent-kauran-19-oic acid and of 16beta,17-hydroxy-ent-kauran-19-oic acid are also new. Diterpenes are reported here for the first time in the large genus Vernonia. Their structures were elucidated using 1D and 2D NMR measurement as well as ESI, CIMS, and HRMS analysis. Two hirsutinolides were studied for their NF-kappaB DNA binding activity in HaCaT cells (a human cell line similar to keratinocytes) and for their inhibition on IL-8 production in HeLa cells.
    Phytochemistry 01/2006; 67(1):62-9. · 3.35 Impact Factor
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    ABSTRACT: Enteric Yersinia bacteria trigger transcription and secretion of the proinflammatory chemokines interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) in epithelial cells. Both chemokines are controlled by NF-kappaB. The NF-kappaB-binding site in the IL-8 promoter preferentially binds Rel p65/p65 homodimers and p50/p65 heterodimers while the NF-kappaB-binding motifs of the MCP-1 promoter preferably bind p50/p65 heterodimers and p50/p50 homodimers. Sesquiterpene lactones inhibit the transcription factor NF-kappaB by alkylating the p65 subunit. In this study we investigated the inhibitory effects of sesquiterpene lactones and the NF-kappaB inhibitor SN50 on NF-kappaB p50 and p65 subunits in Yersinia-triggered IL-8 and MCP-1 production. The sesquiterpene lactones blocked Yersinia-triggered IL-8 and MCP-1 production in a dose-dependent manner. In contrast, SN50 inhibited IL-8 production at high concentrations whereas it diminished the amount of secreted MCP-1 significantly already at low concentrations. By means of electrophoretic mobility shift assays we demonstrate that sesquiterpene lactones inhibit Yersinia-triggered activation of NF-kappaB by inhibiting Rel p65, but not Rel p50. Our results also demonstrate that SN50 is useful for inhibition of nuclear translocation of the NF-kappaB p50 subunit but cannot be considered a general NF-kappaB inhibitor.
    International Journal of Medical Microbiology 01/2006; 295(8):531-8. · 4.54 Impact Factor
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    ABSTRACT: Phospholipases A(2) (PLA(2)) are important constituents of snake venoms, being responsible for several of their toxic actions. Extracts from plants used in folk medicine were screened for inhibition of the enzymatic activity of myotoxin I, a PLA(2) from Bothrops asper. Piper umbellatum and Piper peltatum extracts tested positive, and their fractionation resulted in the isolation of 4-nerolidylcatechol. Its inhibitory effects towards toxic activities of two Bothrops myotoxins, representing catalytically active (Asp49) and catalytically inactive (Lys49) types of group II PLA(2)s, respectively, were characterized. The enzyme activity of B. asper myotoxin I was completely inhibited by 4-nerolidylcatechol at an inhibitor:toxin ratio of 10:1 (wt/wt) with an IC50 of approximately 1mM. In addition, 4-nerolidylcatechol inhibited representatives of groups I and III of PLA(2)s. Its preincubation with Bothrops myotoxins significantly reduced their myotoxic and edema-inducing activities in animal experiments. However, when 4-nerolidylcatechol was administered in situ, immediately after toxin injection, its inhibitory ability was substantially lower or negligible. This might be explained by the rapid action of these toxins in vivo, together with the slow inactivation of PLA(2) activity observed in vitro. Electrophoretic and chromatographic analyses of myotoxins ruled out major changes in protein charge, hydrophobicity, or gross molecular mass being involved in the inhibition mechanism. Mass spectrometry determinations are consistent with the covalent modification of myotoxin by one molecule of 4-nerolidylcatechol. Finally, a novel compound was isolated from both Piper species, sharing the nerolidyl skeleton, but nevertheless not being inhibitory towards the PLA(2)s studied.
    Phytochemistry 06/2005; 66(9):1017-25. · 3.35 Impact Factor
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    ABSTRACT: Four new hopane-type saponins, glinusides F, G, H, and I (1-4), and the known succulentoside B (5), as well as the two known flavones 5,7,4'-trihydroxyflavone-6,8-di-C-glucoside (vicenin-2) and 5,7,4'-trihydroxyflavone-8-C-sophoroside (vitexin-2' '-O-glucoside), were isolated from the seeds of Glinus lotoides growing in Ethiopia. On the basis of the spectroscopic data analysis, including 2D NMR and HRESIMS, the new structures were characterized as 3beta-O-beta-D-xylopyranosyl-6alpha-O-beta-D-xylopyranosyl-16beta-O-beta-D-xylopyranosyl-22-hydroxyhopane (1), 3beta-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-xylopyranosyl-6alpha,16beta-dihydroxy-22-O-alpha-L-rhamnopyranosylhopane (2), 3beta-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-xylopyranosyl-6alpha-O-beta-D-xylopyranosyl-16beta-hydroxy-22-O-alpha-L-rhamnopyranosylhopane (3), and 3beta-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-d-xylopyranosyl-6alpha-O-beta-D-xylopyranosyl-16beta-O-beta-D-xylopyranosyl-22-hopane (4).
    Journal of Natural Products 03/2005; 68(3):443-6. · 3.29 Impact Factor
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    ABSTRACT: Sesquiterpene lactones (SLs) are the active compounds of a variety of traditionally used medicinal plants from the Asteraceae family. They are known to possess a considerable antiinflammatory activity in different inflammation models. They inhibit the transcription factor NF-kappaB probably by alkylating cysteine38 in the DNA binding domain of the p65 subunit. Here we investigate a set of 103 different sesquiterpene lactones representing 6 structural groups (44 germacranolides, 16 heliangolides, 22 guaianolides, 9 pseudoguaianolides, 2 hypocretenolides, 10 eudesmanolides) for their NF-kappaB inhibiting properties and the resulting IC(100)-values were submitted to a QSAR study. Properties important for the inhibition potency are discussed for the whole data set and for subsets of the different structural classes.
    Journal of Medicinal Chemistry 11/2004; 47(24):6042-54. · 5.61 Impact Factor
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    ABSTRACT: The reinvestigation of the aerial parts of Montanoa hibiscifolia afforded four new eudesmanolides (1-4), three of them with a rare endoperoxide structural element and the fourth with a rare carbonyl function. It also afforded three unusual montabibisciolides (5-7), two (5 and 7) of which are new natural compounds. Additionally, seven germacrolides (8-10 and 12-15) and one melampolide (11) could be isolated, including two new germacrolides (8 and 9). Their structures were elucidated using 1D and 2D NMR measurement as well as ESI, CIMS, and HRMS analyses. Low-energy conformations were obtained by molecular mechanics calculations. The (13)C NMR data of five compounds are reported for the first time. Six sesquiterpene lactones (4, 6, 10, 11, 12, and 14) were investigated for their inhibitory activity on DNA binding of the transcription factor NF-kappa B using Jurkat T cells as well as RAW 264.7 cells. Besides the alpha-methylene-gamma-butyrolactone moiety the epoxy group in the acyl residue might take part in the NF-kappa B inhibitory activity of sesquiterpene lactones.
    Journal of Natural Products 05/2004; 67(4):622-30. · 3.29 Impact Factor
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    ABSTRACT: The roots of Croton hirtus (Euphorbiaceae) collected in Paraiso, Cartago (Costa Rica) afforded, in addition to the few known metabolites, 20 new compounds: the bis-nor dolabradane 1, the dolabradanes 2 and 3, the kauranes 4-7, the cyclopropakauranes 8 and 9, the hirtusanes 10-15, the germacradiene esters 16-18 and the C-25 compound 21, presumably formed by a Diels-Alder reaction between compound 18 and a monoterpene. All structures were elucidated using high field 1D and 2D NMR techniques. MS fragmentation patterns are here reported. The absolute configurations of 4 and 9 were elucidated by using circular dichroism. The separation was performed with modern chromatographic technics.
    Revista de biologia tropical 04/2004; 52(1):269-85. · 0.55 Impact Factor

Publication Stats

267 Citations
77.14 Total Impact Points

Institutions

  • 2000–2014
    • University of Costa Rica
      • • Escuela de Química
      • • Centro de Investigaciones en Productos Naturales (CIPRONA)
      San José, San José, Costa Rica
  • 2002–2011
    • University of Freiburg
      • • Institute of Pharmaceutical Sciences
      • • Department of Physical Chemistry
      Freiburg, Baden-Württemberg, Germany