Browsing by Autor "Rodrigo Villagomez"

Now showing 1 - 11 of 11

A method for rapid screening of ketone biotransformations: Detection of whole cell Baeyer–Villiger monooxygenase activity
(Elsevier BV, 2011) Javier A. Linares‐Pastén; Georgina Chávez; Rodrigo Villagomez; Gashaw Mamo; Rajni Hatti‐Kaul
Analytical Methods for Identification and Quantification of Quinoa Saponins: A Review
(American Chemical Society, 2025) Rodrigo Villagomez; Maribel Lozano; Yonny Flores; Yasufumi Kobayashi; Yasunari Fujita; Giovanna R. Almanza
Quinoa saponins (SAPs) are key secondary metabolites occurring as complex mixtures mainly in the seed coat of Chenopodium quinoa Willd. Although traditionally removed due to their bitter taste and potential toxicity, quinoa SAPs display diverse biological activities, including anti-inflammatory, hypocholesterolemic, antifungal, molluscicidal, hemolytic, and cytotoxic effects, that support their potential applications in pharmaceuticals, functional foods, cosmetics, and biopesticides. Their amphiphilic nature also enables their use as natural emulsifiers. This review (1981-2024) summarizes advances in analytical methodologies for quinoa SAPs, emphasizing that while GC-MS and LC-MS/MS are widely applied for profiling, full structural elucidation still requires isolation and analysis by NMR and MS. We discuss key considerations for quinoa SAPs identification using GC-MS, LC-MS/MS, and NMR. Quantification remains challenging and is often based on relative estimations, with afrosymmetric, UV-vis, and GC-MS methods being the most frequently employed, while HPLC-DAD, LC-MS, and GC-MS/MS offer greater sensitivity. Ultimately, the selection of the analytical method and standard critically determines accuracy.
Anti-cancer stem cell activity of a sesquiterpene lactone isolated from Ambrosia arborescens and of a synthetic derivative
(Public Library of Science, 2017) Wendy Soria Sotillo; Rodrigo Villagomez; Sandra Smiljanic; Xiaoli Huang; Atena Malakpour; Sebastian Kempengren; Gloria Rodrigo; Giovanna R. Almanza; Olov Sterner; Stina Oredsson
New regimens are constantly being pursued in cancer treatment, especially in the context of treatment-resistant cancer stem cells (CSCs) that are assumed to be involved in cancer recurrence. Here, we investigated the anti-cancer activity of sesquiterpene lactones (SLs) isolated from Ambrosia arborescens and of synthetic derivatives in breast cancer cell lines, with a specific focus on activity against CSCs. The breast cancer cell lines MCF-7, JIMT-1, and HCC1937 and the normal-like breast epithelial cell line MCF-10A were treated with the SLs damsin and coronopilin, isolated from A. arborescens, and with ambrosin and dindol-01, synthesized using damsin. Inhibitory concentration 50 (IC50) values were obtained from dose-response curves. Based on IC50 values, doses in the μM range were used for investigating effects on cell proliferation, cell cycle phase distribution, cell death, micronuclei formation, and cell migration. Western blot analysis was used to investigate proteins involved in cell cycle regulation as well as in the NF-κB pathway since SLs have been shown to inhibit this transcription factor. Specific CSC effects were investigated using three CSC assays. All compounds inhibited cell proliferation; however, damsin and ambrosin were toxic at single-digit micromolar ranges, while higher concentrations were required for coronopilin and dindol-01. Of the four cell lines, the compounds had the least effect on the normal-like MCF-10A cells. The inhibition of cell proliferation can partly be explained by downregulation of cyclin-dependent kinase 2. All compounds inhibited tumour necrosis factor-α-induced translocation of NF-κB from the cytoplasm to the nucleus. Damsin and ambrosin treatment increased the number of micronuclei; moreover, another sign of DNA damage was the increased level of p53. Treatment with damsin and ambrosin decreased the CSC subpopulation and inhibited cell migration. Our results suggest that these compounds should be further investigated to find efficient CSC-inhibiting compounds.
Antioxidant and Antimutagenic Polyisoprenylated Benzophenones and Xanthones from Rheedia acuminata
(SAGE Publishing, 2011) Giovanna R. Almanza; Raúl Quispe; Patricia Mollinedo; Gloria Rodrigo; Ery Odette Fukushima; Rodrigo Villagomez; Björn Åkesson; Olov Sterner
Dichloromethane extract of the stem bark of Rheedia acuminata yielded three benzophenones with antioxidant activity, the new one named acuminophenone A (1), guttiferone K (2) and isoxanthochymol (3), along with the known xanthones formoxanthone C (4) and macluraxanthone (5). The structures were established through interpretation of their spectroscopic data, the stereochemistry of compounds (1) and (2) were resolved by experimental and computational experiments and their antioxidant activities were measured using the DPPH, ABTS and TEAC assays. The antioxidant results showed that metabolites 1, 4 and 5 had a better antioxidant activity than the reference compound quercetin. In addition, we evaluate the mutagenicity and antimutagenicity of the CH2Cl2 extract as well as of the free radical scavenger compounds 1, 4 and 5 by the AMES Salmonella/microsomal test. No mutagenicity was found in the CH2Cl2 extract using Salmonella typhimurium strains TA98, TA100, TA102, TA1537 and TA1538, with or without S9 metabolic activation. The pure compounds neither showed mutagenicity in TA 102 strain and the most important result was the strong reduction of mutagenic effect induced by hydrogen peroxide in S. typhimurium TA102, with or without S9, showed by the compounds 1 (more than 93%) and 4 (more than 88%) at 0.02 microg/plate.
Effect of Natural and Semisynthetic Pseudoguianolides on the Stability of NF-κB:DNA Complex Studied by Agarose Gel Electrophoresis
(Public Library of Science, 2015) Rodrigo Villagomez; Rajni Hatti‐Kaul; Olov Sterner; Giovanna R. Almanza; Javier A. Linares‐Pastén
The nuclear factor κB (NF-κB) is a promising target for drug discovery. NF-κB is a heterodimeric complex of RelA and p50 subunits that interact with the DNA, regulating the expression of several genes; its dysregulation can trigger diverse diseases including inflammation, immunodeficiency, and cancer. There is some experimental evidence, based on whole cells studies, that natural sesquiterpene lactones (Sls) can inhibit the interaction of NF-κB with DNA, by alkylating the RelA subunit via a Michael addition. In the present work, 28 natural and semisynthetic pseudoguianolides were screened as potential inhibitors of NF-κB in a biochemical assay that was designed using pure NF-κB heterodimer, pseudoguianolides and a ~1000 bp palindromic DNA fragment harboring two NF-κB recognition sequences. By comparing the relative amount of free DNA fragment to the NF-κB - DNA complex, in a routine agarose gel electrophoresis, the destabilizing effect of a compound on the complex is estimated. The results of the assay and the following structure-activity relationship study, allowed the identification of several relevant structural features in the pseudoguaianolide skeleton, which are necessary to enhance the dissociating capacity of NF-κB-DNA complex. The most active compounds are substituted at C-3 (α-carbonyl), in addition to having the α-methylene-γ-lactone moiety which is essential for the alkylation of RelA.
Extraction of Glucuronoarabinoxylan from Quinoa Stalks (Chenopodium quinoa Willd.) and Evaluation of Xylooligosaccharides Produced by GH10 and GH11 Xylanases
(American Chemical Society, 2017) Daniel Martín Salas-Veizaga; Rodrigo Villagomez; Javier A. Linares‐Pastén; Cristhian Carrasco; María Teresa Álvarez; Patrick Adlercreutz; Eva Nordberg Karlsson
Byproducts from quinoa are not yet well explored sources of hemicellulose or products thereof. In this work, xylan from milled quinoa stalks was retrieved to 66% recovery by akaline extraction using 0.5 M NaOH at 80 °C, followed by ethanol precipitation. The isolated polymer eluted as a single peak in size-exclusion chromatography with a molecular weight of >700 kDa. Analysis by Fourier transform infrared spectroscopy and nuclear magnetic resonance (NMR) combined with acid hydrolysis to monomers showed that the polymer was built of a backbone of β(1 → 4)-linked xylose residues that were substituted by 4-O-methylglucuronic acids, arabinose, and galactose in an approximate molar ratio of 114:23:5:1. NMR analysis also indicated the presence of α(1 → 5)-linked arabinose substituents in dimeric or oligomeric forms. The main xylooligosaccharides (XOs) produced after hydrolysis of the extracted glucuronoarabinoxylan polymer by thermostable glycoside hydrolases (GHs) from families 10 and 11 were xylobiose and xylotriose, followed by peaks of putative substituted XOs. Quantification of the unsubstituted XOs using standards showed that the highest yield from the soluble glucuronoarabinoxylan fraction was 1.26 g/100 g of xylan fraction, only slightly higher than the yield (1.00 g/100 g of xylan fraction) from the insoluble fraction (p < 0.05). No difference in yield was found between reactions in buffer or water (p > 0.05). This study shows that quinoa stalks represent a novel source of glucuronoarabinoxylan, with a substituent structure that allowed for limited production of XOs by GH10 or GH11 enzymes.
Microwave-Assisted Semisynthesis and Leishmanicidal Activity of Some Phenolic Constituents from Lichens
(Multidisciplinary Digital Publishing Institute, 2023) Grover Castañeta; Rodrigo Villagomez; Efraín Salamanca; Pamela Canaviri-Paz; José A. Bravo; José L. Vila; Daniela Bárcenas-Pérez; José Cheel; Beatriz Sepúlveda; Alberto Giménez
Leishmaniasis is considered one of the most untreated tropical diseases in the world. In this study, we investigated the in vitro leishmanicidal activity and cytotoxicity of various isolated lichen substances, including atranorin (1), usnic acid (2), gyrophoric acid (3), salazinic acid (4), galbinic acid (5), and parietin (6), and some semi-synthetic imine derivatives of usnic acid (7, 8, 9) and atranorin (10, 11, 12, 13). Imine condensation reactions with hydrazine and several amines were assisted by microwave heating, an efficient and eco-friendly energy source. The most interesting result was obtained for compound 2, which has high leishmanicidal activity but also high cytotoxicity. This cytotoxicity was mitigated in its derivative, 9, with better selectivity and high antileishmanic activity. This result may indicate that the usnic acid derivative (9) obtained using condensation with two cyclohexylamine groups is a promising lead compound for the discovery of new semisynthetic antiparasitic drugs.
Natural and Semi-Synthetic Pseudoguaianolides as Inhibitors of NF-κB
(Scientific Research Publishing, 2014) Rodrigo Villagomez; Juan A. Collado; Eduardo Muñóz; Giovanna R. Almanza; Olov Sterner
Damsin (1) is a natural pseudoguaianolide sesquiterpene that inhibits NF-κB, a protein complex that controls the transcription of DNA in mammalian cells, and has a potential for standing model for the development of new anti-cancer lead structures. In order to do a preliminary structure-activity study and improve the anti-cancer activity, fourteen derivatives and analogs were prepared and evaluated. These were chosen to represent both structural diversity and structural novelty. The importance of α methylene-γ-lactone moiety for the anti-cancer activity was confirmed, even though other features in the scaffold were shown to be important for the activity. In some cases a new substitution negatively affected the initial activity, however, two analogues, indolo [3,2-c]-4-desoxydamsin (5) and ambrosin (6), were found to be more potent.
PICTORIAL MECHANISTIC VIEWS ON THE CHEMICAL HISTORY OF WITHAFERIN A: THE STRUCTURAL DETERMINATION OF THE SIDE CHAIN, THE ORGANIC CHEMISTRY NOTEBOOK SERIES, A DIDACTICAL APPROACH, Nº 16
(2022) Rodrigo Villagomez; José L. Vila; José A. Bravo
This article is an approach to the historical development of the structural elucidation of organic natural substances that began with chemical degradations, isotopic labeling processes and sometimes synthesis, all chemical reactions. We used the work of Lavie et al. in: “Constituents of Withania somnifera Dun. III. The side chain of Withaferin A” as the study-object, complemented by other bibliographic material, and we proposed mechanistic routes of each reaction used by the authors. The objective was to explain these processes from the didactic point of view of reaction mechanisms
Selective Cytotoxicity of Dams in Derivatives in Breast Cancer Cells
(2019) Maribel Lozano; Maribel Lozano; Wendy Soria; Wendy Soria; Giovanna R. Almanza; Sophie Manner; Stina Oredsson; Rodrigo Villagomez; Olov Sterner
Cancer is the leading cause of death worldwide, and there is a constant need for new treatment strategies. Sesquiterpene lactones containing a 3-methylenedihydrofuran-2(3H)-one (or a-methylene-g-lactone) moiety, for example damsin (1), are Michael acceptors that affect biological processes such as cell proliferation, death/apoptosis, and cell migration, by interfering with cell signalling pathways. Although the reactivity of the α-methylene-γ-lactone moiety is important for these effects, the Michael addition is reversible and it can be assumed that also other parts of the molecules will moderate any given biological activity. In this investigation, the cytotoxicity of 23 a-methylene-g-lactones towards normal breast epithelial MCF-10A cells as well as breast cancer JIMT-1 cells is compared. Most of the investigated compounds are semisynthetic derivatives prepared by the condensation of the natural product damsin (1) with aldehydes. The two cell lines were treated with various concentrations of the compounds in dose response assays, and the 50 % inhibitory concentration (IC50) was determined from dose response curves. The IC50 values were found to depend strongly on the overall structure. The ratio between the IC50 values for MCF-10A and JIMT-1 cells, as a measure for the selectivity of a compound to kill cancer cells, was calculated, and found to vary between just over 1 to more than 10. The most potent derivatives formed from the condensation of 1 with aromatic aldehydes towards JIMT-1 cells are 3a and 3i, both with ratios between the IC50 values for MCF-10A and JIMT-1 cells close to 5. Also some aldol condensation products with acyclic aldehydes, i.e. 3r and 3u, were equally potent, and the latter showed the highest selectivity (ratio > 10). Structure-activity relationships that may explain the observed differences in potency and selectivity are discussed.
Sesquiterpene lactones from Ambrosia arborescens Mill. inhibit pro-inflammatory cytokine expression and modulate NF-κB signaling in human skin cells
(Elsevier BV, 2018) Daniel Svensson; Maribel Lozano; Giovanna R. Almanza; Bengt‐Olof Nilsson; Olov Sterner; Rodrigo Villagomez