Renato Murillo

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

Are you Renato Murillo?

Claim your profile

Publications (37)104.82 Total impact

  • [Show abstract] [Hide abstract]
    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 05/2014; 19(5):6727-6736. DOI:10.3390/molecules19056727 · 2.34 Impact Factor
  • Source
    [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; 77(3). DOI:10.1021/np400672g · 3.95 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: The rainforest is an important source of natural compounds with therapeutic properties. Although there are many anti-inflammatory and antineoplastic drugs available to the clinician, there is an ongoing need for new therapeutic drugs with fewer serious adverse effects. Aim: To evaluate the in vitro cytotoxic effects of lupeol and casearin G on tumor cells, on phagocytic activity and nitric oxide (NO) production by blood mononuclear cells. Material and Methods: The cytotoxic effect of these compounds on cell lines MCF-7 (human breast adenocarcinoma) and PC-3 (human prostate cancer) was measured by a colorimetric assay (MTS/PMS) and the sulphorhodamine B assay. Peripheral blood mononuclear cells were obtained from eight healthy volunteers. The effect of these compounds on nitric oxide (NO) production was measured using the Griess reaction. Their effect on phagocytic activity of PBMC was also evaluated. Results: Lupeol (≥ 2 mM) resulted in a reduction of both the phagocytic index and the percentage of phagocytic monocytes and macrophages. Treatment of monocytes/macrophages with lupeol (72 µM) and casearin G (4 µM) reduced the production of NO. Neither lupeol (< 969 µM) nor casearin G (< 55 µM) had cytotoxic effects on PBMC. Casearin G showed both cytotoxic (IC50, LC50) and cytostatic (GI50) effects against tumor cells, PC-3 (IC50 = 12.5 µM; GI50 = 13.3 µM; LC50 = 51.9 µM) and MCF-7 (IC50 = 112.8 µM; GI50 = 11.8 µM; LC50 = 49.4 µM), as well as a hemolytic effect (≥ 182 µM). Conclusions: These observations indicate that lupeol and casearin G might be useful compounds in the preparation of anti-inflammatory drugs, whereas casearin G might be useful in the elaboration of antitumor drugs.
    Revista medica de Chile 09/2013; 141(9):1150-7. DOI:10.4067/S0034-98872013000900007 · 0.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The majority of snakebite envenomations in Central America are caused by the viperid species Bothrops asper, whose venom contains a high proportion of zinc-dependent metalloproteinases that play a relevant role in the pathogenesis of hemorrhage characteristic of these envenomations. Broad metalloproteinase inhibitors, such as the peptidomimetic hydroxamate Batimastat, have been shown to inhibit snake venom metalloproteinases (SVMP). However, the difficulty in having open public access to Batimastat and similar molecules highlights the need to design new inhibitors of SVMPs that could be applied in the treatment of snakebite envenomations. We have chosen the SVMP BaP1 as a model to search for new inhibitors using different strategies, that is, screening of the Prestwick Chemical Library and rational peptide design. Results from these approaches provide clues on the structural requirements for efficient BaP1 inhibition and pave the way for the design of new inhibitors of SVMP.
    ACS Medicinal Chemistry Letters 06/2012; 3(7). DOI:10.1021/ml300068r · 3.07 Impact Factor
  • [Show abstract] [Hide abstract]
    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). DOI:10.1002/hlca.201100127 · 1.39 Impact Factor
  • [Show abstract] [Hide abstract]
    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. DOI:10.1016/j.bmc.2011.06.067 · 2.95 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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. DOI:10.1021/np200158g · 3.95 Impact Factor
  • [Show abstract] [Hide abstract]
    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. DOI:10.1021/np100523s · 3.95 Impact Factor
  • Planta Medica 08/2010; 76(12). DOI:10.1055/s-0030-1264260 · 2.34 Impact Factor
  • Planta Medica 08/2010; 76(12). DOI:10.1055/s-0030-1264187 · 2.34 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Phenalinolactones are novel terpene glycoside antibiotics produced by Streptomyces sp. Tü6071. Inactivation of three oxygenase genes (plaO2, plaO3 and plaO5), two dehydrogenase genes (plaU, plaZ) and one putative acetyltransferase gene (plaV) led to the production of novel phenalinolactone derivatives (PL HS6, PL HS7, PL HS2 and PL X1). Furthermore, the exact biosynthetic functions of two enzymes were determined, and their in vitro activities were demonstrated. PlaO1, an Fe(II)/alpha-ketoglutarate-dependent dioxygenase, is responsible for the key step in gamma-butyrolactone formation, whereas PlaO5, a cytochrome P450-dependent monooxygenase, catalyses the 1-C-hydroxylation of phenalinolactone D. In addition, stable isotope feeding experiments with biosynthetic precursors shed light on the origin of the carbons in the gamma-butyrolactone moiety.
    ChemBioChem 07/2010; 11(10):1383-91. DOI:10.1002/cbic.201000117 · 3.06 Impact Factor
  • Omar A Dupuy, Renato Murillo, José A Bonilla
    [Show abstract] [Hide abstract]
    ABSTRACT: Different species of the Asteraceae family are a potential source of sesquiterpene lactones with anti-inflammatory properties. Macrophages play a central role in the regulation of immune responses. In the present study, the in vitro effect of two sesquiterpene lactones, a millerenolide and a thieleanin, was assessed by measuring the production of nitric oxide (NO) by cell line RAW (murine macrophages) using the Griess reagent. Additionally, the effect of these sesquiterpene lactones on phagocytic capacity of latex particles and the reduction of nitroblue tetrazolium (NBT) were evaluated microscopically. Treatment of macrophages with > 2.5 microg/ml of both sesquiterpene lactones, reduced the production of NO. A decreased number of macrophages able to reduce NBT were observed when these cells were treated with 3 microg/ml of millerenolide or 7.5 microg/ml of thieleanin. Treatment of macrophages with 4 microg/ml ofmillerenolide or 7.5 microg/ml of thieleanin, reduced the phagocytic capacity of macrophages. Cytotoxic effects on the macrophages were only observed when the concentration was increased to 8 microg/ml of millerenolide or 25 microg/ml of thieleanin. Our results suggest that these sesquiterpene lactones could be useful compounds in the elaboration of anti-inflammatory drugs.
    Revista de biologia tropical 09/2008; 56(3):1063-73. · 0.61 Impact Factor
  • Revista de biologia tropical 09/2008; 56(3):1043-1051. DOI:10.15517/rbt.v56i3.5691 · 0.61 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The present study was carried out in order to examine the anticancer properties of two sesquiterpene lactones, millerenolide and thieleanin, isolated from Viguiera sylvatica and Decachaeta thieleana, against cell lines in vitro, and on the growth B16/BL6 melanoma tumors in C57BL/6 mice. Millerenolide and thieleanin showed a similar pattern of cytotoxicity with the greatest effect on viability being evident with A549 human lung cancer cells (IC(50) - 40 and 32 microM respectively), and with the 3T3/HER2 cell line which are 3T3 mouse fibroblasts transfected with the HER2 oncogene (IC(50) - 16 and 28 microM respectively). The parent 3T3 cells and the B16/BL6 mouse melanoma cells were less sensitive to these compounds, with thieleanin showing an IC(50) with B16/BL6 greater than the highest dose tested (203 microM). Treatment with millerenolide (8 mg/kg, i.p. on days 0, 2 and 4 post-inoculation) significantly inhibited the growth of subcutaneous B16/BL6 tumors in C57BL/6 mice, (50% inhibition at day 25, P=0.015), as well as retarding the appearance of detectable tumor (millerenolide - day 15.2+/-0.4 vs control - day 12.8+/-0.5, mean+/-SEM, P=0.011). In contrast, treatment with thieleanin (8 mg/kg every other day up to the day of kill) neither retarded the appearance of the tumor nor its growth.
    Fitoterapia 07/2008; 79(6):428-32. DOI:10.1016/j.fitote.2007.07.019 · 2.22 Impact Factor
  • [Show abstract] [Hide abstract]
    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. DOI:10.1021/jm701318x · 5.48 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Natural products are used in the production of therapeutic drugs due to their wide diversity and excellent adaptability to biological structures. Sesquiterpene lactones are the active constituents of several plants from the Asteraceae family. To assess the in vitro effect of a sesquiterpene lactone (millerenolide). The drug effect was assessed measuring the proliferation of lymphocytes using the 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonylJ-2H-tetrazolium hydroxide (XTT) technique. Changes on the cell cycle were analyzed on a FACSort flow cytometer The effect of millerenolide on the production of nitric oxide (NO) by macrophages was evaluated using the Griess reagent. Additionally, phagocytosis of latex particles and nitroblue tetrazolium (NBT) reduction by macrophages were evaluated microscopically. Treatment of human peripheral blood mononuclear cells (PBMC) with millerenolide decreases the proliferation of lymphocytes, decreases the percentage of cells in S, and G2/M phases, and increases the proportion of cells in GO/Gl phase. Treatment of macrophages with millerenolide, reduces the production of NO, the phagocytic capacity and the number of cells able to reduce NBT. Cytotoxic effects of the lactone on human PBMC were only observed when the concentration was increased to 6 microg/ml. Millerenolide could be considered as a potential therapeutic agent with immunosuppressive properties.
    Revista medica de Chile 02/2008; 136(1):64-72. · 0.37 Impact Factor
  • Source
    Revista medica de Chile 01/2008; 136(1). DOI:10.4067/S0034-98872008000100008 · 0.37 Impact Factor
  • [Show abstract] [Hide abstract]
    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. DOI:10.1007/s10495-006-0331-2 · 3.61 Impact Factor
  • Source
  • [Show abstract] [Hide abstract]
    ABSTRACT: Phenalinolactones are terpene glycosides with antibacterial activity. A striking structural feature is a highly oxidized gamma-butyrolactone of elusive biosynthetic origin. To investigate the genetic basis of the phenalinolactones biosynthesis, we cloned and sequenced the corresponding gene cluster from the producer strain Streptomyces sp. Tü6071. Spanning a 42 kbp region, 35 candidate genes could be assigned to putatively encode biosynthetic, regulatory, and resistance-conferring functions. Targeted gene inactivations were carried out to specifically manipulate the phenalinolactones pathway. The inactivation of a sugar methyltransferase gene and a cytochrome P450 monoxygenase gene led to the production of modified phenalinolactone derivatives. The inactivation of a Fe(II)/alpha-ketoglutarate-dependent dioxygenase gene disrupted the biosynthetic pathway within gamma-butyrolactone formation. The structure elucidation of the accumulating intermediate indicated that pyruvate is the biosynthetic precursor of the gamma butyrolactone moiety.
    Chemistry & Biology 05/2006; 13(4):365-77. DOI:10.1016/j.chembiol.2006.01.011 · 6.59 Impact Factor

Publication Stats

657 Citations
104.82 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
  • 2000–2005
    • University of Freiburg
      • Institute of Pharmaceutical Sciences
      Freiburg, Baden-Württemberg, Germany