Chemico-Biological Interactions

The antioxidant activity of nine lichen substances, including methylatrarate (1), methyl haematommate (2), lobaric acid (3), fumarprotocetraric acid (4), sphaerophorin (5), subsphaeric acid (6), diffractaic acid (7), barbatolic acid (8) and salazinic acid (9) has been determined through cyclic volta...

Full description

Autores:
Yañez, Osvaldo
Osorio, Manuel I.
Osorio, Edison
Tiznado, William
Hernández Cortes Lina María
García, Camilo
Nagles, Orlando
Simirgiotis, Mario J.
Castañeta, Grover
Areche, Carlos
García-Beltrán, Olimpo
Tipo de recurso:
Article of investigation
Fecha de publicación:
2023
Institución:
Universidad de Ibagué
Repositorio:
Repositorio Universidad de Ibagué
Idioma:
eng
OAI Identifier:
oai:repositorio.unibague.edu.co:20.500.12313/5576
Acceso en línea:
https://hdl.handle.net/20.500.12313/5576
Palabra clave:
Sustancias de líquenes - Actividad antioxidante
Sustancias de líquenes - Actividad enzimática
voltametría cíclica y teórica
Antioxidant
Cyclic voltamperograms
CYPs enzymes
DFT methods
Lichenic substances
Natural products
Rights
openAccess
License
© 2023 The Authors
id UNIBAGUE2_68d75b0824dcf5eabcc0f24fc3b986f7
oai_identifier_str oai:repositorio.unibague.edu.co:20.500.12313/5576
network_acronym_str UNIBAGUE2
network_name_str Repositorio Universidad de Ibagué
repository_id_str
dc.title.eng.fl_str_mv Chemico-Biological Interactions
title Chemico-Biological Interactions
spellingShingle Chemico-Biological Interactions
Sustancias de líquenes - Actividad antioxidante
Sustancias de líquenes - Actividad enzimática
voltametría cíclica y teórica
Antioxidant
Cyclic voltamperograms
CYPs enzymes
DFT methods
Lichenic substances
Natural products
title_short Chemico-Biological Interactions
title_full Chemico-Biological Interactions
title_fullStr Chemico-Biological Interactions
title_full_unstemmed Chemico-Biological Interactions
title_sort Chemico-Biological Interactions
dc.creator.fl_str_mv Yañez, Osvaldo
Osorio, Manuel I.
Osorio, Edison
Tiznado, William
Hernández Cortes Lina María
García, Camilo
Nagles, Orlando
Simirgiotis, Mario J.
Castañeta, Grover
Areche, Carlos
García-Beltrán, Olimpo
dc.contributor.author.none.fl_str_mv Yañez, Osvaldo
Osorio, Manuel I.
Osorio, Edison
Tiznado, William
Hernández Cortes Lina María
García, Camilo
Nagles, Orlando
Simirgiotis, Mario J.
Castañeta, Grover
Areche, Carlos
García-Beltrán, Olimpo
dc.subject.armarc.none.fl_str_mv Sustancias de líquenes - Actividad antioxidante
Sustancias de líquenes - Actividad enzimática
voltametría cíclica y teórica
topic Sustancias de líquenes - Actividad antioxidante
Sustancias de líquenes - Actividad enzimática
voltametría cíclica y teórica
Antioxidant
Cyclic voltamperograms
CYPs enzymes
DFT methods
Lichenic substances
Natural products
dc.subject.proposal.eng.fl_str_mv Antioxidant
Cyclic voltamperograms
CYPs enzymes
DFT methods
Lichenic substances
Natural products
description The antioxidant activity of nine lichen substances, including methylatrarate (1), methyl haematommate (2), lobaric acid (3), fumarprotocetraric acid (4), sphaerophorin (5), subsphaeric acid (6), diffractaic acid (7), barbatolic acid (8) and salazinic acid (9) has been determined through cyclic voltammetry. The compounds 1–4 presented slopes close to the Nernst constant of 0.059 V, indicating a 2H+/2e− relation between protons and electrons, as long as the compounds 5, 6, 7, 8, and 9 present slopes between 0.037 V and 0.032 V, indicating a 1H+/2e− relation between protons and electrons. These results show a high free radical scavenging activity by means of the release of H+, suggesting an important antioxidant capacity of these molecules. Theoretical calculations of hydrogen bond dissociation enthalpies (BDE), proton affinities (PA), and Proton Transfer (PT) mechanisms, at M06-2x/6-311+G(d,p) level complement the experimental results. Computations support that the best antioxidant activity is obtained for the molecules (3, 4, 5, 6, 7 and 8), that have a carboxylic acid group close to a phenolic hydroxyl group, through hydrogen atomic transfer (HAT) and sequential proton loss electron transfer (SPLET) mechanisms. Additional computations were performed for modelling binding affinity of the lichen substances with CYPs enzymes, mainly CYP1A2, CYP51, and CYP2C9*2 isoforms, showing strong affinity for all the compounds described in this study.
publishDate 2023
dc.date.issued.none.fl_str_mv 2023-02-25
dc.date.accessioned.none.fl_str_mv 2025-08-29T22:47:48Z
dc.date.available.none.fl_str_mv 2025-08-29T22:47:48Z
dc.type.none.fl_str_mv Artículo de revista
dc.type.coar.none.fl_str_mv http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.coarversion.none.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.content.none.fl_str_mv Text
dc.type.driver.none.fl_str_mv info:eu-repo/semantics/article
dc.type.version.none.fl_str_mv info:eu-repo/semantics/publishedVersion
format http://purl.org/coar/resource_type/c_2df8fbb1
status_str publishedVersion
dc.identifier.citation.none.fl_str_mv Yañez, O., Osorio, M., Osorio, E., Tiznado, W., Ruíz, L., García, C., Nagles, O., Simirgiotis, M., Castañeta, G., Areche, C. y García-Beltrán, O. (2023). Antioxidant activity and enzymatic of lichen substances: A study based on cyclic voltammetry and theoretical. Chemico-Biological Interactions, 372, 110357. DOI: 10.1016/j.cbi.2023.110357
dc.identifier.doi.none.fl_str_mv 10.1016/j.cbi.2023.110357
dc.identifier.eissn.none.fl_str_mv 18727786
dc.identifier.issn.none.fl_str_mv 00092797
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/20.500.12313/5576
identifier_str_mv Yañez, O., Osorio, M., Osorio, E., Tiznado, W., Ruíz, L., García, C., Nagles, O., Simirgiotis, M., Castañeta, G., Areche, C. y García-Beltrán, O. (2023). Antioxidant activity and enzymatic of lichen substances: A study based on cyclic voltammetry and theoretical. Chemico-Biological Interactions, 372, 110357. DOI: 10.1016/j.cbi.2023.110357
10.1016/j.cbi.2023.110357
18727786
00092797
url https://hdl.handle.net/20.500.12313/5576
dc.language.iso.none.fl_str_mv eng
language eng
dc.relation.citationstartpage.none.fl_str_mv 110357
dc.relation.citationvolume.none.fl_str_mv 372
dc.relation.ispartofjournal.none.fl_str_mv Chemico-Biological Interactions
dc.relation.references.none.fl_str_mv V. Kagan, E. Serbinova, K. Novikov, V. Ritov, Y. Kozlov, T. Stoytchev, Toxic and protective effects of antioxidants in biomembranes, Arch. Toxicol. 59 (1986) 302–305, https://doi.org/10.1007/978-3-642-71248-7_51.
P.A.S. White, R.C.M. Oliveira, A.P. Oliveira, M.R. Serafini, A.A.S. Araújo, D. P. Gelain, J.C.F. Moreira, J.R.G.S. Almeida, J.S.S. Quintans, L.J. Quintans-Junior, M.R.V. Santos, Antioxidant activity and mechanisms of action of natural compounds isolated from lichens: a systematic review, Molecules 19 (2014) 14496–14527, https://doi.org/10.3390/molecules190914496.
J.M. McCord, The evolution of free radicals and oxidative stress, Am. J. Med. 108 (2000) 652–659, https://doi.org/10.1016/S0002-9343(00)00412-5
C. Trautwein, S.L. Friedman, D. Schuppan, M. Pinzani, Hepatic fibrosis: concept to treatment, J. Hepatol. 62 (2015) S15–S24, https://doi.org/10.1016/j. jhep.2015.02.039
A. Torres-Benítez, M. Rivera-Montalvo, B. Sepúlveda, O.N. Castro, E. Nagles, M. J. Simirgiotis, O. Garcia-Beltr ´ an, ´ C. Areche, Metabolomic analysis of two parmotrema lichens: P. Robustum (Degel.) hale and P. Andinum (mull. Rg.) hale using UHPLC-ESI-OT-MS-MS, Molecules (2017), https://doi.org/10.3390/ molecules2211186
J. Boustie, S. Tomasi, M. Grube, Bioactive lichen metabolites: alpine habitats as an untapped source, Phytochemistry Rev. 10 (2011) 287–307, https://doi.org/ 10.1007/s11101-0
I. Gülçin, M. Oktay, O.I. ¨ Küfrevioǧlu, A. Aslan, Determination of antioxidant activity of lichen Cetraria islandica (L) Ach, J. Ethnopharmacol. 79 (2002) 325–329, https://doi.org/10.1016/S0378-8741(01)00396-8.
M. Kosani´c, B. Rankoví, Lichens as possible sources of antioxidants, Pak. J. Pharm. Sci. 24 (201
B. Paudel, H.D. Bhattarai, D.P. Pandey, J.S. Hur, S.G. Hong, I.C. Kim, J.H. Yim, Antioxidant, antibacterial activity and brine shrimp toxicity test of some mountainous lichens from Nepal, Biol. Res. 45 (2012) 387–391, https://doi.org/ 10.4067/S0716-976020120004000
B. Rankovi´c, M. Kosani´c, N. Manojlovi´c, A. Ranˇci´c, T. Stanojkovi´c, Chemical composition of Hypogymnia physodes lichen and biological activities of some its major metabolites, Med. Chem. Res. 23 (2014) 408–416, https://doi.org/10.1007/ s00044-013-0644-y
M. Kosani´c, N. Manojlovi´c, S. Jankovi´c, T. Stanojkovi´c, B. Rankovi´c, Evernia prunastri and Pseudoevernia furfuraceae lichens and their major metabolites as antioxidant, antimicrobial and anticancer agents, Food Chem. Toxicol. 53 (2013) 112–118, https://doi.org/10.1016/j.fct.2012.11.034.
F. Salgado, L. Albornoz, C. Cort´ez, E. Stashenko, K. Urrea-Vallejo, E. Nagles, C. Galicia-Virviescas, A. Cornejo, A. Ardiles, M. Simirgiotis, O. García-Beltr´ an, C. Areche, Secondary metabolite profiling of species of the genus usnea by UHPLCESI-OT-MS-MS, Molecules (2018), https://doi.org/10.3390/molecules23010054
V. Shukla, G.P. Joshi, M.S.M. Rawat, Lichens as a potential natural source of bioactive compounds: a review, Phytochemistry Rev. 9 (2010) 303–314, https:// doi.org/10.1007/s1
C. Areche, J.R. Parra, B. Sepulveda, O. García-Beltran, ´ M.J. Simirgiotis, UHPLC-MS metabolomic fingerprinting, antioxidant, and enzyme inhibition activities of Himantormia lugubris from Antarctica, Metabolites 12 (2022) 560, https://doi. org/10.3390/metabo12060560.
V.B. Tatipamula, S.S.P. Annam, Antimycobacterial activity of acetone extract and isolated metabolites from folklore medicinal lichen Usnea laevis Nyl. against drugsensitive and multidrug-resistant tuberculosis strains, J. Ethnopharmacol. 282 (2022), 114641, https://doi.org/10.1016/j.jep.2021.114641.
L. Fagnani, L. Nazzicone, P. Bellio, N. Franceschini, D. Tondi, A. Verri, S. Petricca, R. Iorio, G. Amicosante, M. Perilli, G. Celenza, Protocetraric and salazinic acids as potential inhibitors of SARS-CoV-2 3CL Protease: biochemical, cytotoxic, and computational characterization of depsidones as slow-binding inactivators, Pharmaceuticals 15 (2022) 714, https://doi.org/10.3390/ph15060714
A. Kocovic, J. Jeremic, J. Bradic, M. Sovrlic, J. Tomovic, P. Vasiljevic, M. Andjic, N. Draginic, M. Grujovic, K. Mladenovic, D. Baskic, S. Popovic, S. Matic, V. Zivkovic, N. Jeremic, V. Jakovljevic, N. Manojlovic, Phytochemical analysis, antioxidant, antimicrobial, and cytotoxic activity of different extracts of xanthoparmelia stenophylla lichen from stara planina, Serbia, Plants 11 (2022) 1624, https://doi.org/10.3390/plants11131624
T.K. Kim, J.M. Hong, K.H. Kim, S.J. Han, I.C. Kim, H. Oh, J.H. Yim, Potential of ramalin and its derivatives for the treatment of alzheimer’s disease, Molecules 26 (2021) 1–12, https://doi.org/10.3390/molecules26216445.
K. Moln´ ar, E. Farkas, Current results on biological activities of lichen secondary metabolites: a review, Zeitschrift Fur Naturforsch. - Sect. C J. Biosci. 65 (2010) 157–173, https://doi.org/10.1515/znc-2010-3-401
A.S. Nugraha, L.F. Untari, A. Laub, A. Porzel, K. Franke, L.A. Wessjohann, Anthelmintic and antimicrobial activities of three new depsides and ten known depsides and phenols from Indonesian lichen: parmelia cetrata Ach, Nat. Prod. Res. 35 (2021) 5001–5010, https://doi.org/10.1080/14786419.2020.1761361.
T.H. Do, T.H. Duong, H.T. Nguyen, T.H. Nguyen, J. Sichaem, C.H. Nguyen, H. H. Nguyen, N.P. Long, Article biological activities of lichen-derived monoaromatic compounds, Molecules 27 (2022), https://doi.org/10.3390/molecules27092871.
M.S. Brewer, Natural antioxidants: sources, compounds, mechanisms of action, and potential applications, Compr. Rev. Food Sci. Food Saf. 10 (2011) 221–247, https://doi.org/10.1111/j.1541-4337.2011.00156.x
E. Osorio, J.K. Olson, W. Tiznado, A.I. Boldyrev, Analysis of why boron avoids sp 2 hybridization and classical structures in the B nH n+2 series, Chem. Eur J. 18 (2012) 9677–9681, https://doi.org/10.1002/chem.201200506.
G.W. Burton, T. Doba, E. Gabe, L. Hughes, F.L. Lee, L. Prasad, K.U. Ingold, Autoxidation of biological molecules. 4. Maximizing the antioxidant activity of phenols, J. Am. Chem. Soc. 107 (1985) 7053–7065, https://doi.org/10.1021/ ja00310a049.
M.C. Foti, C. Daquino, C. Geraci, Electron-transfer reaction of cinnamic acids and their methyl esters with the DPPH. Radical in alcoholic solutions, J. Org. Chem. 69 (2004) 2309–2314, https://doi.org/10.1021/jo035758q.
C. Areche, B.K. Cassels, W. Tiznado, Structure – Antioxidant Activity Relationships in Boldine and Glaucine : a DFT Study †, 2021, pp. 590–596, https://doi.org/ 10.1039/d0nj04
A. Vasquez-Espinal, ´ O. Yanez, ˜ E. Osorio, C. Areche, O. García-Beltr´ an, L.M. Ruiz, B. K. Cassels, W. Tiznado, Theoretical study of the antioxidant activity of quercetin oxidation products, Front. Chem. 7 (2019), https://doi.org/10.3389/ fchem.2019.00818
E. Osorio, E.G. P´erez, C. Areche, L.M. Ruiz, B.K. Cassels, E. Florez, ´ Why Is Quercetin a Better Antioxidant than Taxifolin ? Theoretical Study of Mechanisms Involving Activated Forms, 2013, pp. 2165–2172, https://doi.org/10.1007/ s00894-012-1732-5
F. Salgado, J. Caballero, R. Vargas, A. Cornejo, C. Areche, Continental and Antarctic Lichens: isolation, identification and molecular modeling of the depside tenuiorin from the Antarctic lichen Umbilicaria Antarctica as tau protein inhibitor, Nat. Prod. Res. 34 (2020) 646–650, https://doi.org/10.1080/ 14786419.2018.1492576
C. Gonz´ alez, C. Cartagena, L. Caballero, F. Melo, C. Areche, A. Cornejo, The fumarprotocetraric acid inhibits tau covalently, avoiding cytotoxicity of aggregates in cells, Molecules 26 (2021) 1–11, https://doi.org/10.3390/molecules26123760.
T.K. Shameera Ahamed, V.K. Rajan, K. Sabira, K. Muraleedharan, DFT and QTAIM based investigation on the structure and antioxidant behavior of lichen substances Atranorin, Evernic acid and Diffractaic acid, Comput. Biol. Chem. 80 (2019) 66–78, https://doi.org/10.1016/j.compbiolchem.2019.03.009.
R. Krishnan, J.S. Binkley, R. Seeger, J.A. Pople, Self-consistent molecular orbital methods. XX. A basis set for correlated wave functions, J. Chem. Phys. 72 (1980) 650–654, https://doi.org/10.1063/1.438955.
A.D. McLean, G.S. Chandler, Contracted Gaussian basis sets for molecular calculations. I. Second row atoms, Z=11-18, J. Chem. Phys. 72 (1980) 5639–5648, https://doi.org/10.1063/1.438980.
M.J. Frisch, G.W. Trucks, H.E. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, G. Scalmani, V. Barone, G.A. Petersson, F. O, J.B. Foresman, J.D. Fox, Gaussian 16, Gaussian, Inc., Wallingford CT, 2
S.V. Jovanovic, S. Steenken, M. Tosic, B. Marjanovic, M.G. Simic, Flavonoids as antioxidants, J. Am. Chem. Soc. 116 (1994) 4846–4851, https://doi.org/10.1021/ ja00090a0
J.E. Bartmess, Thermodynamics of the electron and the proton, J. Phys. Chem. 98 (1994) 6420–6424, https://doi.org/10.1021/j100076a029.
] S. Sansen, J.K. Yano, R.L. Reynald, G.A. Schoch, K.J. Griffin, C.D. Stout, E. F. Johnson, Adaptations for the oxidation of polycyclic aromatic hydrocarbons exhibited by the structure of human P450 1A2, J. Biol. Chem. 282 (2007) 14348–14355, https://doi.org/10.1074/jbc.M611692200
T.Y. Hargrove, L. Friggeri, Z. Wawrzak, A. Qi, W.J. Hoekstra, R.J. Schotzinger, J. D. York, F. Peter Guengerich, G.I. Lepesheva, Structural analyses of Candida albicans sterol 14α-demethylase complexed with azole drugs address the molecular basis of azole-mediated inhibition of fungal sterol biosynthesis, J. Biol. Chem. 292 (2017) 6728–6743, https://doi.org/10.1074/jbc.M117.778308.
S.J. Parikh, C.M. Evans, J.O. Obi, Q. Zhang, K. Maekawa, K.C. Glass, M.B. Shah, Structure of cytochrome P450 2C9*2 in complex with losartan: insights into the effect of genetic polymorphism, Mol. Pharmacol. 98 (2020) 529–539, https://doi. org/10.1124/MOLPHARM.120
RCSB PDB - 7OW9, Crystal structure of a staphylococcal orthologue of CYP134A1 (CYPX) in complex with Cyclo-L-leucyl-L-leucine (n.d.), https://www.rcsb. org/structure/7OW9. (Accessed 31 Janua
H.M. Berman, J. Westbrook, Z. Feng, G. Gilliland, T.N. Bhat, H. Weissig, I. N. Shindyalov, P.E. Bourne, The protein Data Bank, Nucleic Acids Res. 28 (2000) 235–242, https://doi.org/10.1093/nar/28.1.235.
O. Trott, A. Olson, AutoDock Vina, Improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading, J. Comput. Chem. 31 (2010) 455–461, https://doi.org/10.1002/jcc.21334.
J.J.P. Stewart, MOPAC, 2016.
J.J.P. Stewart, Optimization of parameters for semiempirical methods V: modification of NDDO approximations and application to 70 elements, J. Mol. Model. 13 (2007) 1173–1213, https://doi.org/10.1007/s00894-007-0233-4.
J. Rez ˇ ´ aˇc, P. Hobza, Advanced corrections of hydrogen bonding and dispersion for semiempirical quantum mechanical methods, J. Chem. Theor. Comput. 8 (2012) 141–151, https://doi.org/10.1021/ct200751e.
M. Banck, T. Vandermeersch, N.M. O’Boyle, G.R. Hutchison, C. Morley, C. A. James, Open Babel, An open chemical toolbox, J. Cheminf. 3 (2011) 33, https:// doi.org/10.1186/1758-29
G. Madhavi Sastry, M. Adzhigirey, T. Day, R. Annabhimoju, W. Sherman, Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments, J. Comput. Aided Mol. Des. 27 (2013) 221–234, https://doi.org/ 10.1007/s10822-013-9644-8
G.M. Morris, D.S. Goodsell, R.S. Halliday, R. Huey, W.E. Hart, R.K. Belew, A. J. Olson, Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function, J. Comput. Chem. 19 (1998) 1639–1662, https://doi.org/10.1002/(SICI)1096-987X(19981115)19:14<1639::AIDJCC10>3.0.CO;2-B.
Dassault Syst`emes BIOVIA, Discovery Studio Modeling Environment, 2017.
E.R. Johnson, S. Keinan, P. Mori-S´ anchez, J. Contreras-García, A.J. Cohen, W. Yang, Revealing noncovalent interactions, J. Am. Chem. Soc. 132 (2010) 6498–6506, https://doi.org/10.1021/ja100936w.
J. Contreras-García, E.R. Johnson, S. Keinan, R. Chaudret, J.-P. Piquemal, D. N. Beratan, W. Yang, NCIPLOT: a program for plotting noncovalent interaction regions, J. Chem. Theor. Comput. 7 (2011) 625–632, https://doi.org/10.1021/ ct100641a
W. Humphrey, A. Dalke, K. Schulten, VMD: visual molecular dynamics, J. Mol. Graph. 14 (1996) 33–38, https://doi.org/10.1016/0263-7855(96)00018-5.
C. Abad-Zapatero, Ligand efficiency indices for effective drug discovery, Expet Opin. Drug Discov. 2 (2007) 469–488, https://doi.org/10.1517/ 17460441.2.4.469.
C. Abad-Zapatero, O. Periˇsi´c, J. Wass, A.P. Bento, J. Overington, B. Al-Lazikani, M. E. Johnson, Ligand efficiency indices for an effective mapping of chemicobiological space: the concept of an atlas-like representation, Drug Discov. Today 15 (2010) 804–811, https://doi.org/10.1016/J.DRUDIS.2010.08.004.
C. Abad-Zapatero, Ligand Efficiency Indices for Drug Discovery, Academic Press, San Diego, 2013, https://doi.org/10.1016/B978-0-12-404635-1.00009-8.
C.H. Reynolds, B.A. Tounge, S.D. Bembenek, Ligand binding efficiency: trends, physical basis, and implications, J. Med. Chem. 51 (2008) 2432–2438, https://doi. org/10.1021/jm7012
M.M. Cavalluzzi, G.F. Mangiatordi, O. Nicolotti, G. Lentini, Ligand efficiency metrics in drug discovery: the pros and cons from a practical perspective, Expet Opin. Drug Discov. 12 (2017) 1087–1104, https://doi.org/10.1080/ 17460441.2017.1365056
D.F. Veber, S.R. Johnson, H.-Y. Cheng, B.R. Smith, K.W. Ward, K.D. Kopple, Molecular properties that influence the oral bioavailability of drug candidates, J. Med. Chem. 45 (2002) 2615–2623, https://doi.org/10.1021/jm020017n.
A. Daina, O. Michielin, V. Zoete, SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules, Sci. Rep. 7 (2017) 1–13, https://doi.org/10.1038/srep42717
A.J. Blasco, A.G. Crevill´en, M.C. Gonzalez, ´ A. Escarpa, Direct electrochemical sensing and detection of natural antioxidants and antioxidant capacity in vitro systems, Electroanalysis 19 (2007) 2275–2286, https://doi.org/10.1002/ elan.200704004
G. Ziyatdinova, E. Kozlova, H. Budnikov, Electropolymerized eugenol-MWNTbased electrode for voltammetric evaluation of wine antioxidant capacity, Electroanalysis 27 (2015) 1660–1668, https://doi.org/10.1002/elan.201400712.
J.O. Miners, D.J. Birkett, Cytochrome P4502C9: an enzyme of major importance in human drug metabolism, Br. J. Clin. Pharmacol. 45 (1998) 525–538, https://doi. org/10.1046/j.1365-2
dc.rights.eng.fl_str_mv © 2023 The Authors
dc.rights.accessrights.none.fl_str_mv info:eu-repo/semantics/openAccess
dc.rights.coar.none.fl_str_mv http://purl.org/coar/access_right/c_abf2
dc.rights.license.none.fl_str_mv Atribución-NoComercial 4.0 Internacional (CC BY-NC 4.0)
dc.rights.uri.none.fl_str_mv https://creativecommons.org/licenses/by-nc/4.0/
rights_invalid_str_mv © 2023 The Authors
http://purl.org/coar/access_right/c_abf2
Atribución-NoComercial 4.0 Internacional (CC BY-NC 4.0)
https://creativecommons.org/licenses/by-nc/4.0/
eu_rights_str_mv openAccess
dc.format.mimetype.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier Ireland Ltd
dc.publisher.place.none.fl_str_mv Irlanda
publisher.none.fl_str_mv Elsevier Ireland Ltd
dc.source.none.fl_str_mv https://www.sciencedirect.com/science/article/pii/S0009279723000248
institution Universidad de Ibagué
bitstream.url.fl_str_mv https://repositorio.unibague.edu.co/bitstreams/7781353d-8586-49ce-b0fb-7f81ac99c339/download
https://repositorio.unibague.edu.co/bitstreams/7638422c-ed4e-4c67-8ec0-d409ba1c9f38/download
https://repositorio.unibague.edu.co/bitstreams/dc277581-a0db-4abd-83dd-d071352ef569/download
https://repositorio.unibague.edu.co/bitstreams/d789836a-1ed8-4d66-8710-a0e921850a73/download
bitstream.checksum.fl_str_mv b080281428fc6bd7d8e5135913f7c66f
508248b078f621952d499114191ddcc8
2fa3e590786b9c0f3ceba1b9656b7ac3
058f85e48ee7b4a63978f44f740cdce8
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
MD5
repository.name.fl_str_mv Repositorio Institucional Universidad de Ibagué
repository.mail.fl_str_mv bdigital@metabiblioteca.com
_version_ 1851059978850271232
spelling Yañez, Osvaldo2cf4e584-65f4-4612-a255-91946983e93a-1Osorio, Manuel I.55eb1036-fdba-448e-8089-0b4e0e904398-1Osorio, Edisone6d834e4-46ca-40f0-ab7c-630a35856901-1Tiznado, William608d766a-6be4-4e17-84ce-3392c57ab23e-1Hernández Cortes Lina María0a1c338e-7398-44d3-bbc4-36f9d4fc1124600García, Camiloa242acd0-27fc-4f74-9edf-a79f4a8315af-1Nagles, Orlandofb5423b9-9352-4b81-bbfa-8cb00924403b-1Simirgiotis, Mario J.fba227f7-8a32-43c0-bed2-f40fdc666832-1Castañeta, Groverf6ce73da-22f5-4391-958a-7fa62c5429b9-1Areche, Carlosb6d8fc85-e264-4a47-b13b-f39b0ae610ab-1García-Beltrán, Olimpo6037fb1a-6bfc-4342-9fa2-54cdb7c4e977-12025-08-29T22:47:48Z2025-08-29T22:47:48Z2023-02-25The antioxidant activity of nine lichen substances, including methylatrarate (1), methyl haematommate (2), lobaric acid (3), fumarprotocetraric acid (4), sphaerophorin (5), subsphaeric acid (6), diffractaic acid (7), barbatolic acid (8) and salazinic acid (9) has been determined through cyclic voltammetry. The compounds 1–4 presented slopes close to the Nernst constant of 0.059 V, indicating a 2H+/2e− relation between protons and electrons, as long as the compounds 5, 6, 7, 8, and 9 present slopes between 0.037 V and 0.032 V, indicating a 1H+/2e− relation between protons and electrons. These results show a high free radical scavenging activity by means of the release of H+, suggesting an important antioxidant capacity of these molecules. Theoretical calculations of hydrogen bond dissociation enthalpies (BDE), proton affinities (PA), and Proton Transfer (PT) mechanisms, at M06-2x/6-311+G(d,p) level complement the experimental results. Computations support that the best antioxidant activity is obtained for the molecules (3, 4, 5, 6, 7 and 8), that have a carboxylic acid group close to a phenolic hydroxyl group, through hydrogen atomic transfer (HAT) and sequential proton loss electron transfer (SPLET) mechanisms. Additional computations were performed for modelling binding affinity of the lichen substances with CYPs enzymes, mainly CYP1A2, CYP51, and CYP2C9*2 isoforms, showing strong affinity for all the compounds described in this study.application/pdfYañez, O., Osorio, M., Osorio, E., Tiznado, W., Ruíz, L., García, C., Nagles, O., Simirgiotis, M., Castañeta, G., Areche, C. y García-Beltrán, O. (2023). Antioxidant activity and enzymatic of lichen substances: A study based on cyclic voltammetry and theoretical. Chemico-Biological Interactions, 372, 110357. DOI: 10.1016/j.cbi.2023.11035710.1016/j.cbi.2023.1103571872778600092797https://hdl.handle.net/20.500.12313/5576engElsevier Ireland LtdIrlanda110357372Chemico-Biological InteractionsV. Kagan, E. Serbinova, K. Novikov, V. Ritov, Y. Kozlov, T. Stoytchev, Toxic and protective effects of antioxidants in biomembranes, Arch. Toxicol. 59 (1986) 302–305, https://doi.org/10.1007/978-3-642-71248-7_51.P.A.S. White, R.C.M. Oliveira, A.P. Oliveira, M.R. Serafini, A.A.S. Araújo, D. P. Gelain, J.C.F. Moreira, J.R.G.S. Almeida, J.S.S. Quintans, L.J. Quintans-Junior, M.R.V. Santos, Antioxidant activity and mechanisms of action of natural compounds isolated from lichens: a systematic review, Molecules 19 (2014) 14496–14527, https://doi.org/10.3390/molecules190914496.J.M. McCord, The evolution of free radicals and oxidative stress, Am. J. Med. 108 (2000) 652–659, https://doi.org/10.1016/S0002-9343(00)00412-5C. Trautwein, S.L. Friedman, D. Schuppan, M. Pinzani, Hepatic fibrosis: concept to treatment, J. Hepatol. 62 (2015) S15–S24, https://doi.org/10.1016/j. jhep.2015.02.039A. Torres-Benítez, M. Rivera-Montalvo, B. Sepúlveda, O.N. Castro, E. Nagles, M. J. Simirgiotis, O. Garcia-Beltr ´ an, ´ C. Areche, Metabolomic analysis of two parmotrema lichens: P. Robustum (Degel.) hale and P. Andinum (mull. Rg.) hale using UHPLC-ESI-OT-MS-MS, Molecules (2017), https://doi.org/10.3390/ molecules2211186J. Boustie, S. Tomasi, M. Grube, Bioactive lichen metabolites: alpine habitats as an untapped source, Phytochemistry Rev. 10 (2011) 287–307, https://doi.org/ 10.1007/s11101-0I. Gülçin, M. Oktay, O.I. ¨ Küfrevioǧlu, A. Aslan, Determination of antioxidant activity of lichen Cetraria islandica (L) Ach, J. Ethnopharmacol. 79 (2002) 325–329, https://doi.org/10.1016/S0378-8741(01)00396-8.M. Kosani´c, B. Rankoví, Lichens as possible sources of antioxidants, Pak. J. Pharm. Sci. 24 (201B. Paudel, H.D. Bhattarai, D.P. Pandey, J.S. Hur, S.G. Hong, I.C. Kim, J.H. Yim, Antioxidant, antibacterial activity and brine shrimp toxicity test of some mountainous lichens from Nepal, Biol. Res. 45 (2012) 387–391, https://doi.org/ 10.4067/S0716-976020120004000B. Rankovi´c, M. Kosani´c, N. Manojlovi´c, A. Ranˇci´c, T. Stanojkovi´c, Chemical composition of Hypogymnia physodes lichen and biological activities of some its major metabolites, Med. Chem. Res. 23 (2014) 408–416, https://doi.org/10.1007/ s00044-013-0644-yM. Kosani´c, N. Manojlovi´c, S. Jankovi´c, T. Stanojkovi´c, B. Rankovi´c, Evernia prunastri and Pseudoevernia furfuraceae lichens and their major metabolites as antioxidant, antimicrobial and anticancer agents, Food Chem. Toxicol. 53 (2013) 112–118, https://doi.org/10.1016/j.fct.2012.11.034.F. Salgado, L. Albornoz, C. Cort´ez, E. Stashenko, K. Urrea-Vallejo, E. Nagles, C. Galicia-Virviescas, A. Cornejo, A. Ardiles, M. Simirgiotis, O. García-Beltr´ an, C. Areche, Secondary metabolite profiling of species of the genus usnea by UHPLCESI-OT-MS-MS, Molecules (2018), https://doi.org/10.3390/molecules23010054V. Shukla, G.P. Joshi, M.S.M. Rawat, Lichens as a potential natural source of bioactive compounds: a review, Phytochemistry Rev. 9 (2010) 303–314, https:// doi.org/10.1007/s1C. Areche, J.R. Parra, B. Sepulveda, O. García-Beltran, ´ M.J. Simirgiotis, UHPLC-MS metabolomic fingerprinting, antioxidant, and enzyme inhibition activities of Himantormia lugubris from Antarctica, Metabolites 12 (2022) 560, https://doi. org/10.3390/metabo12060560.V.B. Tatipamula, S.S.P. Annam, Antimycobacterial activity of acetone extract and isolated metabolites from folklore medicinal lichen Usnea laevis Nyl. against drugsensitive and multidrug-resistant tuberculosis strains, J. Ethnopharmacol. 282 (2022), 114641, https://doi.org/10.1016/j.jep.2021.114641.L. Fagnani, L. Nazzicone, P. Bellio, N. Franceschini, D. Tondi, A. Verri, S. Petricca, R. Iorio, G. Amicosante, M. Perilli, G. Celenza, Protocetraric and salazinic acids as potential inhibitors of SARS-CoV-2 3CL Protease: biochemical, cytotoxic, and computational characterization of depsidones as slow-binding inactivators, Pharmaceuticals 15 (2022) 714, https://doi.org/10.3390/ph15060714A. Kocovic, J. Jeremic, J. Bradic, M. Sovrlic, J. Tomovic, P. Vasiljevic, M. Andjic, N. Draginic, M. Grujovic, K. Mladenovic, D. Baskic, S. Popovic, S. Matic, V. Zivkovic, N. Jeremic, V. Jakovljevic, N. Manojlovic, Phytochemical analysis, antioxidant, antimicrobial, and cytotoxic activity of different extracts of xanthoparmelia stenophylla lichen from stara planina, Serbia, Plants 11 (2022) 1624, https://doi.org/10.3390/plants11131624T.K. Kim, J.M. Hong, K.H. Kim, S.J. Han, I.C. Kim, H. Oh, J.H. Yim, Potential of ramalin and its derivatives for the treatment of alzheimer’s disease, Molecules 26 (2021) 1–12, https://doi.org/10.3390/molecules26216445.K. Moln´ ar, E. Farkas, Current results on biological activities of lichen secondary metabolites: a review, Zeitschrift Fur Naturforsch. - Sect. C J. Biosci. 65 (2010) 157–173, https://doi.org/10.1515/znc-2010-3-401A.S. Nugraha, L.F. Untari, A. Laub, A. Porzel, K. Franke, L.A. Wessjohann, Anthelmintic and antimicrobial activities of three new depsides and ten known depsides and phenols from Indonesian lichen: parmelia cetrata Ach, Nat. Prod. Res. 35 (2021) 5001–5010, https://doi.org/10.1080/14786419.2020.1761361.T.H. Do, T.H. Duong, H.T. Nguyen, T.H. Nguyen, J. Sichaem, C.H. Nguyen, H. H. Nguyen, N.P. Long, Article biological activities of lichen-derived monoaromatic compounds, Molecules 27 (2022), https://doi.org/10.3390/molecules27092871.M.S. Brewer, Natural antioxidants: sources, compounds, mechanisms of action, and potential applications, Compr. Rev. Food Sci. Food Saf. 10 (2011) 221–247, https://doi.org/10.1111/j.1541-4337.2011.00156.xE. Osorio, J.K. Olson, W. Tiznado, A.I. Boldyrev, Analysis of why boron avoids sp 2 hybridization and classical structures in the B nH n+2 series, Chem. Eur J. 18 (2012) 9677–9681, https://doi.org/10.1002/chem.201200506.G.W. Burton, T. Doba, E. Gabe, L. Hughes, F.L. Lee, L. Prasad, K.U. Ingold, Autoxidation of biological molecules. 4. Maximizing the antioxidant activity of phenols, J. Am. Chem. Soc. 107 (1985) 7053–7065, https://doi.org/10.1021/ ja00310a049.M.C. Foti, C. Daquino, C. Geraci, Electron-transfer reaction of cinnamic acids and their methyl esters with the DPPH. Radical in alcoholic solutions, J. Org. Chem. 69 (2004) 2309–2314, https://doi.org/10.1021/jo035758q.C. Areche, B.K. Cassels, W. Tiznado, Structure – Antioxidant Activity Relationships in Boldine and Glaucine : a DFT Study †, 2021, pp. 590–596, https://doi.org/ 10.1039/d0nj04A. Vasquez-Espinal, ´ O. Yanez, ˜ E. Osorio, C. Areche, O. García-Beltr´ an, L.M. Ruiz, B. K. Cassels, W. Tiznado, Theoretical study of the antioxidant activity of quercetin oxidation products, Front. Chem. 7 (2019), https://doi.org/10.3389/ fchem.2019.00818E. Osorio, E.G. P´erez, C. Areche, L.M. Ruiz, B.K. Cassels, E. Florez, ´ Why Is Quercetin a Better Antioxidant than Taxifolin ? Theoretical Study of Mechanisms Involving Activated Forms, 2013, pp. 2165–2172, https://doi.org/10.1007/ s00894-012-1732-5F. Salgado, J. Caballero, R. Vargas, A. Cornejo, C. Areche, Continental and Antarctic Lichens: isolation, identification and molecular modeling of the depside tenuiorin from the Antarctic lichen Umbilicaria Antarctica as tau protein inhibitor, Nat. Prod. Res. 34 (2020) 646–650, https://doi.org/10.1080/ 14786419.2018.1492576C. Gonz´ alez, C. Cartagena, L. Caballero, F. Melo, C. Areche, A. Cornejo, The fumarprotocetraric acid inhibits tau covalently, avoiding cytotoxicity of aggregates in cells, Molecules 26 (2021) 1–11, https://doi.org/10.3390/molecules26123760.T.K. Shameera Ahamed, V.K. Rajan, K. Sabira, K. Muraleedharan, DFT and QTAIM based investigation on the structure and antioxidant behavior of lichen substances Atranorin, Evernic acid and Diffractaic acid, Comput. Biol. Chem. 80 (2019) 66–78, https://doi.org/10.1016/j.compbiolchem.2019.03.009.R. Krishnan, J.S. Binkley, R. Seeger, J.A. Pople, Self-consistent molecular orbital methods. XX. A basis set for correlated wave functions, J. Chem. Phys. 72 (1980) 650–654, https://doi.org/10.1063/1.438955.A.D. McLean, G.S. Chandler, Contracted Gaussian basis sets for molecular calculations. I. Second row atoms, Z=11-18, J. Chem. Phys. 72 (1980) 5639–5648, https://doi.org/10.1063/1.438980.M.J. Frisch, G.W. Trucks, H.E. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, G. Scalmani, V. Barone, G.A. Petersson, F. O, J.B. Foresman, J.D. Fox, Gaussian 16, Gaussian, Inc., Wallingford CT, 2S.V. Jovanovic, S. Steenken, M. Tosic, B. Marjanovic, M.G. Simic, Flavonoids as antioxidants, J. Am. Chem. Soc. 116 (1994) 4846–4851, https://doi.org/10.1021/ ja00090a0J.E. Bartmess, Thermodynamics of the electron and the proton, J. Phys. Chem. 98 (1994) 6420–6424, https://doi.org/10.1021/j100076a029.] S. Sansen, J.K. Yano, R.L. Reynald, G.A. Schoch, K.J. Griffin, C.D. Stout, E. F. Johnson, Adaptations for the oxidation of polycyclic aromatic hydrocarbons exhibited by the structure of human P450 1A2, J. Biol. Chem. 282 (2007) 14348–14355, https://doi.org/10.1074/jbc.M611692200T.Y. Hargrove, L. Friggeri, Z. Wawrzak, A. Qi, W.J. Hoekstra, R.J. Schotzinger, J. D. York, F. Peter Guengerich, G.I. Lepesheva, Structural analyses of Candida albicans sterol 14α-demethylase complexed with azole drugs address the molecular basis of azole-mediated inhibition of fungal sterol biosynthesis, J. Biol. Chem. 292 (2017) 6728–6743, https://doi.org/10.1074/jbc.M117.778308.S.J. Parikh, C.M. Evans, J.O. Obi, Q. Zhang, K. Maekawa, K.C. Glass, M.B. Shah, Structure of cytochrome P450 2C9*2 in complex with losartan: insights into the effect of genetic polymorphism, Mol. Pharmacol. 98 (2020) 529–539, https://doi. org/10.1124/MOLPHARM.120RCSB PDB - 7OW9, Crystal structure of a staphylococcal orthologue of CYP134A1 (CYPX) in complex with Cyclo-L-leucyl-L-leucine (n.d.), https://www.rcsb. org/structure/7OW9. (Accessed 31 JanuaH.M. Berman, J. Westbrook, Z. Feng, G. Gilliland, T.N. Bhat, H. Weissig, I. N. Shindyalov, P.E. Bourne, The protein Data Bank, Nucleic Acids Res. 28 (2000) 235–242, https://doi.org/10.1093/nar/28.1.235.O. Trott, A. Olson, AutoDock Vina, Improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading, J. Comput. Chem. 31 (2010) 455–461, https://doi.org/10.1002/jcc.21334.J.J.P. Stewart, MOPAC, 2016.J.J.P. Stewart, Optimization of parameters for semiempirical methods V: modification of NDDO approximations and application to 70 elements, J. Mol. Model. 13 (2007) 1173–1213, https://doi.org/10.1007/s00894-007-0233-4.J. Rez ˇ ´ aˇc, P. Hobza, Advanced corrections of hydrogen bonding and dispersion for semiempirical quantum mechanical methods, J. Chem. Theor. Comput. 8 (2012) 141–151, https://doi.org/10.1021/ct200751e.M. Banck, T. Vandermeersch, N.M. O’Boyle, G.R. Hutchison, C. Morley, C. A. James, Open Babel, An open chemical toolbox, J. Cheminf. 3 (2011) 33, https:// doi.org/10.1186/1758-29G. Madhavi Sastry, M. Adzhigirey, T. Day, R. Annabhimoju, W. Sherman, Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments, J. Comput. Aided Mol. Des. 27 (2013) 221–234, https://doi.org/ 10.1007/s10822-013-9644-8G.M. Morris, D.S. Goodsell, R.S. Halliday, R. Huey, W.E. Hart, R.K. Belew, A. J. Olson, Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function, J. Comput. Chem. 19 (1998) 1639–1662, https://doi.org/10.1002/(SICI)1096-987X(19981115)19:14<1639::AIDJCC10>3.0.CO;2-B.Dassault Syst`emes BIOVIA, Discovery Studio Modeling Environment, 2017.E.R. Johnson, S. Keinan, P. Mori-S´ anchez, J. Contreras-García, A.J. Cohen, W. Yang, Revealing noncovalent interactions, J. Am. Chem. Soc. 132 (2010) 6498–6506, https://doi.org/10.1021/ja100936w.J. Contreras-García, E.R. Johnson, S. Keinan, R. Chaudret, J.-P. Piquemal, D. N. Beratan, W. Yang, NCIPLOT: a program for plotting noncovalent interaction regions, J. Chem. Theor. Comput. 7 (2011) 625–632, https://doi.org/10.1021/ ct100641aW. Humphrey, A. Dalke, K. Schulten, VMD: visual molecular dynamics, J. Mol. Graph. 14 (1996) 33–38, https://doi.org/10.1016/0263-7855(96)00018-5.C. Abad-Zapatero, Ligand efficiency indices for effective drug discovery, Expet Opin. Drug Discov. 2 (2007) 469–488, https://doi.org/10.1517/ 17460441.2.4.469.C. Abad-Zapatero, O. Periˇsi´c, J. Wass, A.P. Bento, J. Overington, B. Al-Lazikani, M. E. Johnson, Ligand efficiency indices for an effective mapping of chemicobiological space: the concept of an atlas-like representation, Drug Discov. Today 15 (2010) 804–811, https://doi.org/10.1016/J.DRUDIS.2010.08.004.C. Abad-Zapatero, Ligand Efficiency Indices for Drug Discovery, Academic Press, San Diego, 2013, https://doi.org/10.1016/B978-0-12-404635-1.00009-8.C.H. Reynolds, B.A. Tounge, S.D. Bembenek, Ligand binding efficiency: trends, physical basis, and implications, J. Med. Chem. 51 (2008) 2432–2438, https://doi. org/10.1021/jm7012M.M. Cavalluzzi, G.F. Mangiatordi, O. Nicolotti, G. Lentini, Ligand efficiency metrics in drug discovery: the pros and cons from a practical perspective, Expet Opin. Drug Discov. 12 (2017) 1087–1104, https://doi.org/10.1080/ 17460441.2017.1365056D.F. Veber, S.R. Johnson, H.-Y. Cheng, B.R. Smith, K.W. Ward, K.D. Kopple, Molecular properties that influence the oral bioavailability of drug candidates, J. Med. Chem. 45 (2002) 2615–2623, https://doi.org/10.1021/jm020017n.A. Daina, O. Michielin, V. Zoete, SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules, Sci. Rep. 7 (2017) 1–13, https://doi.org/10.1038/srep42717A.J. Blasco, A.G. Crevill´en, M.C. Gonzalez, ´ A. Escarpa, Direct electrochemical sensing and detection of natural antioxidants and antioxidant capacity in vitro systems, Electroanalysis 19 (2007) 2275–2286, https://doi.org/10.1002/ elan.200704004G. Ziyatdinova, E. Kozlova, H. Budnikov, Electropolymerized eugenol-MWNTbased electrode for voltammetric evaluation of wine antioxidant capacity, Electroanalysis 27 (2015) 1660–1668, https://doi.org/10.1002/elan.201400712.J.O. Miners, D.J. Birkett, Cytochrome P4502C9: an enzyme of major importance in human drug metabolism, Br. J. Clin. Pharmacol. 45 (1998) 525–538, https://doi. org/10.1046/j.1365-2© 2023 The Authorsinfo:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Atribución-NoComercial 4.0 Internacional (CC BY-NC 4.0)https://creativecommons.org/licenses/by-nc/4.0/https://www.sciencedirect.com/science/article/pii/S0009279723000248Sustancias de líquenes - Actividad antioxidanteSustancias de líquenes - Actividad enzimáticavoltametría cíclica y teóricaAntioxidantCyclic voltamperogramsCYPs enzymesDFT methodsLichenic substancesNatural productsChemico-Biological InteractionsArtículo de revistahttp://purl.org/coar/resource_type/c_2df8fbb1http://purl.org/coar/version/c_970fb48d4fbd8a85Textinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionPublicationTEXTArtículo.pdf.txtArtículo.pdf.txtExtracted texttext/plain4955https://repositorio.unibague.edu.co/bitstreams/7781353d-8586-49ce-b0fb-7f81ac99c339/downloadb080281428fc6bd7d8e5135913f7c66fMD53THUMBNAILArtículo.pdf.jpgArtículo.pdf.jpgIM Thumbnailimage/jpeg27349https://repositorio.unibague.edu.co/bitstreams/7638422c-ed4e-4c67-8ec0-d409ba1c9f38/download508248b078f621952d499114191ddcc8MD54LICENSElicense.txtlicense.txttext/plain; charset=utf-8134https://repositorio.unibague.edu.co/bitstreams/dc277581-a0db-4abd-83dd-d071352ef569/download2fa3e590786b9c0f3ceba1b9656b7ac3MD51ORIGINALArtículo.pdfArtículo.pdfapplication/pdf277246https://repositorio.unibague.edu.co/bitstreams/d789836a-1ed8-4d66-8710-a0e921850a73/download058f85e48ee7b4a63978f44f740cdce8MD5220.500.12313/5576oai:repositorio.unibague.edu.co:20.500.12313/55762025-08-30 03:02:10.279https://creativecommons.org/licenses/by-nc/4.0/© 2023 The Authorshttps://repositorio.unibague.edu.coRepositorio Institucional Universidad de Ibaguébdigital@metabiblioteca.comQ3JlYXRpdmUgQ29tbW9ucyBBdHRyaWJ1dGlvbi1Ob25Db21tZXJjaWFsLU5vRGVyaXZhdGl2ZXMgNC4wIEludGVybmF0aW9uYWwgTGljZW5zZQ0KaHR0cHM6Ly9jcmVhdGl2ZWNvbW1vbnMub3JnL2xpY2Vuc2VzL2J5LW5jLW5kLzQuMC8=

Publicaciones similares