Browsing by Author "Theoduloz, Cristina"

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    ANTIPROLIFERATIVE. ACTIVITY. OF. NEW. 6-BROMINE. DERIVATIVES. OF. 7-ANILINO-1-ARYLISOQUINOLINEQUINONES
    (2016) Ibacache, Juana Andrea; Valderrama Guerrero, Jaime Adolfo; Arancibia Moya, Verónica; Theoduloz, Cristina; Muccioli, Giulio G.
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    Gastroprotective Effect and Cytotoxicity of Labdeneamides with Amino Acids
    (GEORG THIEME VERLAG KG, 2011) Schmeda Hirschmann, Guillermo; Rodriguez, Jaime A.; Theoduloz, Cristina; Valderrama, Jaime A.
    Semisynthetic aromatic amides from Araucaria araucana diterpene acids have been shown to display a relevant gastroprotective effect with low cytotoxicity. The aim of this work was to assess the gastroprotective effect of amino acid amides from imbricatolic acid and its 8(9)-en isomer in the ethanol/HCl-induced gastric lesions model in mice as well as to determine the cytotoxicity of the obtained compounds on the following human cell lines: normal lung fibroblasts (MRC-5), gastric adenocarcinoma (AGS), and liver hepatocellular carcinoma (Hep G2). The diterpenes 15-acetoxyimbricatolic acid, its 8(9)-en isomer, 15-hydroxyimbricatolic acid, and the 8(9)-en derivative, bearing a COOH function at C-19, were used as starting compounds. New amides with C-protected amino acids were prepared. The study reports the effect of a single oral administration of either compound 50 min before the induction of gastric lesions by ethanol/HCl. Some 20 amino acid monoamides were obtained. Dose-response experiments on the glycyl derivatives showed that at a single oral dose of 100 mg/kg, the compounds presented an effect comparable to the reference drug lansoprazole at 20 mg/kg and at 50 mg/kg reduced gastric lesions by about 50%. All derivatives obtained in amounts >30 mg were compared at a single oral dose of 50 mg/kg. The best gastroprotective effect was observed for the exomethylene derivatives bearing a valine residue at C-19 either with an acetoxy or free hydroxy group at C-15. The tryptophanyl derivative from the acetate belonging to the 8,9-en series presented selective cytotoxicity against hepatocytes. The glycyl amide of 15-acetoxyimbricatolic acid was the most cytotoxic and less selective compound with IC50 values between 47 and 103 mu M for the studied cell lines. This is the first report on the obtention of semisynthetic amino acid amides from labdane diterpenes.
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    Inhibition of advanced glycation end products and protein oxidation by leaf extracts and phenolics from Chilean bean landraces
    (Wiley, 2022) Ávila, Felipe; Cruz, Nadia; Alarcón-Esposito, Jazmín; Márquez, Katherine; Burgos-Edwards, Alberto; Theoduloz, Cristina; Schmeda-Hirschmann, Guillermo; Nina, Nélida; Paillán, Hernán; Fuentealba Patino, Denis Alberto; Vejar-Vivar, Carmina
    Phenolics can decrease the levels of advanced glycation end products (AGEs) from proteins, but their mechanisms in complex mixtures are poorly understood. Leaf extracts and the main phenolics from Chilean bean (Phaseolus vulgaris) landraces were assessed for their capacity to inhibit AGEs and oxidative modifications on bovine serum albumin incubated with glucose. The leaf extracts of six bean landraces decreased AGEs (fluorescent AGEs and carboxymethyl lysine) and oxidative (Kyn, Di-Tyr, protein carbonyls) modifications. Fluorescent AGEs were characterized by time-resolved techniques. The composition of the extracts was determined by HPLC-DAD-Q-TOF-MS/MS, and the main compounds were quantified by HPLC. Correlations between the levels of AGEs or protein carbonyls with the main phenolics suggested synergic effects of caffeoyl malic acid (CMA) and rutin. The synergic effect was evaluated using mixtures of rutin and CMA, showing a strong decrease in fluorescent AGEs and protein carbonylation compared with the pure single compounds, supporting this finding.
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    Inhibition of advanced glycation end products and protein oxidation by leaf extracts and phenolics from Chilean bean landraces
    (Elsevier Ltd, 2022) Ávila, Felipe; Cruz, Nadia; Alarcón-Esposito, Jazmín; Márquez, Katherine; Burgos-Edwards, Alberto; Theoduloz, Cristina; Schmeda-Hirschmann, Guillermo; Nina, Nélida; Paillán, Hernán; Fuentealba Patino, Denis Alberto; Vejar-Vivar, Carmina
    Phenolics can decrease the levels of advanced glycation end products (AGEs) from proteins, but their mechanisms in complex mixtures are poorly understood. Leaf extracts and the main phenolics from Chilean bean (Phaseolus vulgaris) landraces were assessed for their capacity to inhibit AGEs and oxidative modifications on bovine serum albumin incubated with glucose. The leaf extracts of six bean landraces decreased AGEs (fluorescent AGEs and carboxymethyl lysine) and oxidative (Kyn, Di-Tyr, protein carbonyls) modifications. Fluorescent AGEs were characterized by time-resolved techniques. The composition of the extracts was determined by HPLC-DAD-Q-TOF-MS/MS, and the main compounds were quantified by HPLC. Correlations between the levels of AGEs or protein carbonyls with the main phenolics suggested synergic effects of caffeoyl malic acid (CMA) and rutin. The synergic effect was evaluated using mixtures of rutin and CMA, showing a strong decrease in fluorescent AGEs and protein carbonylation compared with the pure single compounds, supporting this finding.
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    Studies on quinones. Part 40 : Synthesis and cytotoxicity evaluation of anthraquinone epoxides and isomerization products
    (2006) Valderrama Guerrero, Jaime Adolfo; Espinoza, Omar; González, M. Florencia; Tapia Apati, Ricardo; Rodríguez, Jaime A.; Theoduloz, Cristina; Schmeda Hirschmann, G.
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    Studies on quinones. Part 41 : Synthesis and cytotoxicity of isoquinoline-containing polycyclic quinones
    (2006) Valderrama Guerrero, Jaime Adolfo; González, M. Florencia; Pessoa Mahana, Carlos David; Tapia Apati, Ricardo; Fillion, Houda; Pautet, Félix; Rodríguez, Jaime A.; Theoduloz, Cristina; Schmeda Hirschmann, Guillermo
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    Studies on quinones. Part 43: Synthesis and cytotoxic evaluation of polyoxyethylene-containing 1,4-naphthoquinones
    (PERGAMON-ELSEVIER SCIENCE LTD, 2008) Valderrama, Jaime A.; Leiva, Hilda; Rodriguez, Jaime A.; Theoduloz, Cristina; Schmeda Hirshmann, Guillermo
    A series of naphthoquinones 2,3-disubstituted with chlorine and oxyethylene groups have been prepared from 2,3-dichloro- and 2,3-dimethoxy-1,4-naphthoquinone. The members of these series were tested on normal human. broblasts and on a panel of four human cancer cell lines. Antitumor activities, which were in the range of IC50 1.3-89.5 mu M, discussed in terms of LUMO energy, lipophilicity and size of the polyoxyethylene moiety. (C) 2008 Elsevier Ltd. All rights reserved.
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    Studies on quinones. Part 44: Novel angucyclinone N-heterocyclic analogues endowed with antitumoral activity
    (PERGAMON-ELSEVIER SCIENCE LTD, 2008) Valderrama, Jaime A.; Colonelli, Pamela; Vasquez, David; Florencia Gonzalez, M.; Rodriguez, Jaime A.; Theoduloz, Cristina
    In the search for new potentially anticancer drugs, series of angucyclinone aza-analogues containing pyridine and pyridopyridazine rings have been designed and synthesized by a highly efficient sequence involving a one-pot step for the synthesis of tricyclic quinone intermediate and highly regiocontrolled cycloaddition reactions with polarized 1,3-dienes. The new N-heterocyclic angular quinones were evaluated in vitro on normal human. broblasts and on a panel of four distinct human cancer cell lines. All tested compounds showed high to moderate antitumor activity. Among the compounds, those with one and two pyridine moieties fused to the quinone system have shown the best effect. Structure-activity relationships established the main structural requirement for the activity of the new potential anticancer drugs. (C) 2008 Elsevier Ltd. All rights reserved.
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    Studies on quinones. Part 45 : Novel 7-aminoisoquinoline-5,8-quinone derivatives with antitumor properties on cancer cell lines
    (2009) Valderrama Guerrero, Jaime Adolfo; Ibacache, J. Andrea; Arancibia Moya, Verónica; Rodríguez, Jaime; Theoduloz, Cristina
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    Studies on quinones. Part 46. Synthesis and in vitro antitumor evaluation of aminopyrimidoisoquinolinequinones
    (ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, 2010) Vasquez, David; Rodriguez, Jaime A.; Theoduloz, Cristina; Calderon, Pedro Buc; Valderrama, Jaime A.
    In the search of structure-activity relationship studies and to explore the antitumor effect associated with the pyrimidoisoquinolinequinone scaffold, several diversily substituted 8-aminopyrimido[4,5-c] isoquinolinequinones were regioselectively synthesized. Variation in the structure of the nitrogen substituent bonded to the 8-position of the pyrimidoisoquinolinequinone system led to a set of alkylamino-, phenylamino- and alkyphenylamino derivatives. The cytotoxic activity of the aminoquinone derivatives was evaluated in vitro using the MTT colorimetric method against one normal cell line (MRCS lung fibroblasts) and four human cancer cell lines (AGS human gastric adenocarcinoma; SK-MES-1 human lung cancer cells, and J82 human bladder carcinoma; HL-60 human leukemia) in 72-h drug exposure assays. Among the series, five compounds exhibited interesting antitumor activity against AGS human gastric adenocarcinoma and human lung cancer cells. The SAR studies revealed that both the nature of the nitrogen substituent into the quinone ring and the methyl group at the 6-position play key roles in the antitumor activity. (C) 2010 Elsevier Masson SAS. All rights reserved.
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    Studies on quinones. Part 47. Synthesis of novel phenylaminophenanthridinequinones as potential antitumor agents
    (ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, 2011) Valderrama, Jaime A.; Ibacache, Andrea; Rodriguez, Jaime A.; Theoduloz, Cristina; Benites, Julio
    In our search for potential anticancer agents, a series of 8- and 9-phenylamino-3,4-tetrahydro-phenanthridine-1,7,10(2H)-triones with substituent variations at 6-, 8- and 9-positions were prepared using a highly efficient sequence involving: a) solar photoacylation reactions of benzoquinone with arylaldehydes, b) one-pot procedure for the synthesis of 3,4-dihydrophenanthridine-1,7,10(2H)-trione intermediates from acylhydroquinones and c) highly regiocontrolled acid-induced amination reaction of phenanthridinequinones with phenylamines. The members of this series were in vitro evaluated using the KIT colorimetric method against one normal cell line and three human cancer cell lines. The SAR analysis indicates that the location of nitrogen substituents on the quinone nucleus, the presence of methyl, phenyl, furyl and thienyl groups at the 6-position and the aromatization of the angular cyclo-aliphatic ring of the phenylamino-3,4-tetrahydrophenanthridine-1,7,10(2H)-trione pharmacophore play key roles in the antitumor activity. (C) 2011 Elsevier Masson SAS. All rights reserved.
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    Synthesis and Antitumor Evaluation of 6-Aryl-substituted benzo[j]phenanthridine- and Benzo[g]pyrimido[4,5-c]isoquinolinequinones
    (MDPI, 2012) Iribarra, Jennyfer; Vasquez, David; Theoduloz, Cristina; Benites, Julio; Rios, David; Valderrama, Jaime A.
    A variety of novel 6-arylsubstituted benzo[j]phenanthridine-and benzo[g]pyrimido[4,5-c]isoquinolinequinones were synthesized from 1,4-naphthoquinone, aryl-aldehydes and enaminones via a two-step synthetic approach. The cytotoxic activity of the aminoquinone derivatives was evaluated in vitro against one normal cell line (MRC-5 lung fibroblasts) and three human cancer cell lines (AGS human gastric adenocarcinoma; SK-MES-1 human lung cancer cells, and J82 human bladder carcinoma) in 72-h drug exposure assays using the MTT colorimetric method. Structure-activity relationships within the series of angular quinones reveal that the insertion of pyrrol-2-yl and furan-2-yl groups at the 6-position is more significant for the increase of the potency and selectivity index of the pharmacophores.
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    Synthesis and antitumor evaluation of 8-phenylaminopyrimido[4,5-c]isoquinolinequinones
    (PERGAMON-ELSEVIER SCIENCE LTD, 2009) Vasquez, David; Rodriguez, Jaime A.; Theoduloz, Cristina; Verrax, Julien; Calderon, Pedro Buc; Valderrama, Jaime A.
    A series of 8-phenylaminopyrimido[4,5-c]isoquinoline-7,10-quinone derivatives were prepared by regioselective amination reaction of pyrimido[4,5-c] isoquinoline-7,10-quinones with arylamines in the presence of a Lewis acid catalyst. Preliminary evaluation of the members of the series against cancer cell lines and assays of activation of their cytotoxic activity on K562 cells with ascorbic acid are reported. (C) 2009 Elsevier Ltd. All rights reserved.
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    Synthesis and Antitumor Evaluation of Thiophene Analogs of Kigelinone
    (BENTHAM SCIENCE PUBL LTD, 2009) Valderrama, Jaime A.; Espinoza, Omar; Rodriguez, Jaime; Theoduloz, Cristina
    The synthesis of kigelinone thiophene analogs and related naphtho[2,3-b] thiophene-4,9-quinones from 2-substituted 4,7-dimethoxybenzo[b]thiophenes via an oxidative deprotection, Diels-Alder, and oxidative aromatization reaction sequence is reported. The 2-substituted naphtho[2,3-b] thiophene-4,9-quinones display significant antitumor activity in the range IC50 1.1-47 mu M on a panel of four distinct human cancer cell lines.
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    Synthesis and Cytotoxic Activity on Human Cancer Cells of Novel Isoquinolinequinone-Amino Acid Derivatives
    (2016) Valderrama Guerrero, Jaime Adolfo; Delgado Chang, Virginia; Sepúlveda, Sandra; Benites, Julio; Theoduloz, Cristina; Buc Calderón, Pedro; Muccioli, Giulio G.
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    Synthesis and in vitro antiproliferative evaluation of 3-acyl-2-arylamino-1,4-naphthoquinones
    (2014) Ríos, David; Benites, Julio; Torrejón, Felipe; Theoduloz, Cristina; Valderrama Guerrero, Jaime Adolfo
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    Synthesis and in Vitro Cytotoxic Evaluation of Aminoquinones Structurally Related to Marine Isoquinolinequinones
    (2012) Delgado Chang, Virginia; Ibacache, Andrea; Theoduloz, Cristina; Valderrama Guerrero, Jaime Adolfo
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    Synthesis, half-wave potentials and antiproliferative activity of 1-Aryl-substituted aminoisoquinolinequinones
    (2014) Ibacache, Juana Andrea; Delgado Chang, Virginia; Benites, Julio; Theoduloz, Cristina; Arancibia Moya, Verónica; Muccioli, Giulio G.; Valderrama Guerrero, Jaime Adolfo