β-Lapachone analogs with enhanced antiproliferative activity
In this study, we describe the synthesis of a series of α- and β-lapachone containing hydroxyl or methoxyl groups on the benzene ring, by means of the selective acid promoted cyclization of the appropriate lapachol analog. The evaluation of the antiproliferative activity in human solid tumor cell li...
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todo:paper_02235234_v53_n_p264_RiosLuci2023-10-03T15:11:15Z β-Lapachone analogs with enhanced antiproliferative activity Ríos-Luci, C. Bonifazi, E.L. León, L.G. Montero, J.C. Burton, G. Pandiella, A. Misico, R.I. Padrón, J.M. β-Lapachone Antitumor agents Cell cycle Naphthoquinone Structure-activity relationships 2 hydroxy 5 methoxy 3 (3 methylbut 2 enyl)naphthalene 1,4 dione (5 methoxylapachol) 2 hydroxy 7 methoxynaphthalene 1,4 dione (2 hydroxy 7 methoxy 1,4 naphthoquinone 3 hydroxy 6 methoxy 2 (3 methylbut 2 en 1 yl)naphthalene 1,4 dione (7 methoxylapachol) 3,4 dihydro 10 hydroxy 2,2 dimethyl 2h benzo[g]chromene 5,6 dione (10 hydroxy beta lapachone) 3,4 dihydro 10 methoxy 2,2 dimethyl 2h benzo[g]chromene 5,6 dione (10 methoxy beta lapachone) 3,4 dihydro 6 hydroxy 2,2 dimethyl 2h benzo[g]chromene 5,10 dione (6 hydroxy alpha lapachone) 3,4 dihydro 6 hydroxy 2,2 dimethyl 2h benzo[g]chromene 5,10 dione (6 methoxy alpha lapachone) 3,4 dihydro 7 hydroxy 2,2 dimethyl 2h benzo[g]chromene 5,6 dione (7 hydroxy beta lapachone) 3,4 dihydro 7 methoxy 2,2 dimethyl 2h benzo[h]chromene 5,6 dione (7 methoxy beta lapachone) 3,4 dihydro 8 hydroxy 2,2 dimethyl 2h benzo[h]chromene 5,6 dione (8 hydroxy beta lapachone) 3,4 dihydro 8 methoxy 2,2 dimethyl 2h benzo[g]chromene 5,10 dione (8 methoxy alpha lapachone) 3,4 dihydro 8 methoxy 2,2 dimethyl 2h benzo[h]chromene 5,6 dione (8 methoxy beta lapachone) 3,4 dihydro 9 hydroxy 2,2 dimethyl 2h benzo[g]chromene 5,10 dione (9 hydroxy alpha lapachone) 3,4,5,6 tetrahydro 2,2 dimethyl 5,6 dioxo 2h benzo[h]chromen 7 yl pivalate (7 pivaloyl beta lapachone) 7 hydroxy beta lapachone alpha lapachone antineoplastic agent benzene beta lapachone hydroxyl group isomerase inhibitor reactive oxygen metabolite unclassified drug antiproliferative activity article cell cycle cyclization cytotoxicity DNA damage drug synthesis protein expression tumor cell line Antineoplastic Agents Cell Cycle Cell Line, Tumor Cell Proliferation DNA Topoisomerases Humans Naphthoquinones Reactive Oxygen Species Topoisomerase Inhibitors In this study, we describe the synthesis of a series of α- and β-lapachone containing hydroxyl or methoxyl groups on the benzene ring, by means of the selective acid promoted cyclization of the appropriate lapachol analog. The evaluation of the antiproliferative activity in human solid tumor cell lines provided 7-hydroxy-β-lapachone as lead with enhanced activity over the parent drug β-lapachone. Cell cycle studies, protein expression experiments, and reactive oxygen species analysis revealed that, similarly to β-lapachone, ROS formation and DNA damage are critical factors in the cellular toxicity of 7-hydroxy-β-lapachone. © 2012 Elsevier Masson SAS. All rights reserved. Fil:Bonifazi, E.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Burton, G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_02235234_v53_n_p264_RiosLuci |
| institution |
Universidad de Buenos Aires |
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I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
β-Lapachone Antitumor agents Cell cycle Naphthoquinone Structure-activity relationships 2 hydroxy 5 methoxy 3 (3 methylbut 2 enyl)naphthalene 1,4 dione (5 methoxylapachol) 2 hydroxy 7 methoxynaphthalene 1,4 dione (2 hydroxy 7 methoxy 1,4 naphthoquinone 3 hydroxy 6 methoxy 2 (3 methylbut 2 en 1 yl)naphthalene 1,4 dione (7 methoxylapachol) 3,4 dihydro 10 hydroxy 2,2 dimethyl 2h benzo[g]chromene 5,6 dione (10 hydroxy beta lapachone) 3,4 dihydro 10 methoxy 2,2 dimethyl 2h benzo[g]chromene 5,6 dione (10 methoxy beta lapachone) 3,4 dihydro 6 hydroxy 2,2 dimethyl 2h benzo[g]chromene 5,10 dione (6 hydroxy alpha lapachone) 3,4 dihydro 6 hydroxy 2,2 dimethyl 2h benzo[g]chromene 5,10 dione (6 methoxy alpha lapachone) 3,4 dihydro 7 hydroxy 2,2 dimethyl 2h benzo[g]chromene 5,6 dione (7 hydroxy beta lapachone) 3,4 dihydro 7 methoxy 2,2 dimethyl 2h benzo[h]chromene 5,6 dione (7 methoxy beta lapachone) 3,4 dihydro 8 hydroxy 2,2 dimethyl 2h benzo[h]chromene 5,6 dione (8 hydroxy beta lapachone) 3,4 dihydro 8 methoxy 2,2 dimethyl 2h benzo[g]chromene 5,10 dione (8 methoxy alpha lapachone) 3,4 dihydro 8 methoxy 2,2 dimethyl 2h benzo[h]chromene 5,6 dione (8 methoxy beta lapachone) 3,4 dihydro 9 hydroxy 2,2 dimethyl 2h benzo[g]chromene 5,10 dione (9 hydroxy alpha lapachone) 3,4,5,6 tetrahydro 2,2 dimethyl 5,6 dioxo 2h benzo[h]chromen 7 yl pivalate (7 pivaloyl beta lapachone) 7 hydroxy beta lapachone alpha lapachone antineoplastic agent benzene beta lapachone hydroxyl group isomerase inhibitor reactive oxygen metabolite unclassified drug antiproliferative activity article cell cycle cyclization cytotoxicity DNA damage drug synthesis protein expression tumor cell line Antineoplastic Agents Cell Cycle Cell Line, Tumor Cell Proliferation DNA Topoisomerases Humans Naphthoquinones Reactive Oxygen Species Topoisomerase Inhibitors |
| spellingShingle |
β-Lapachone Antitumor agents Cell cycle Naphthoquinone Structure-activity relationships 2 hydroxy 5 methoxy 3 (3 methylbut 2 enyl)naphthalene 1,4 dione (5 methoxylapachol) 2 hydroxy 7 methoxynaphthalene 1,4 dione (2 hydroxy 7 methoxy 1,4 naphthoquinone 3 hydroxy 6 methoxy 2 (3 methylbut 2 en 1 yl)naphthalene 1,4 dione (7 methoxylapachol) 3,4 dihydro 10 hydroxy 2,2 dimethyl 2h benzo[g]chromene 5,6 dione (10 hydroxy beta lapachone) 3,4 dihydro 10 methoxy 2,2 dimethyl 2h benzo[g]chromene 5,6 dione (10 methoxy beta lapachone) 3,4 dihydro 6 hydroxy 2,2 dimethyl 2h benzo[g]chromene 5,10 dione (6 hydroxy alpha lapachone) 3,4 dihydro 6 hydroxy 2,2 dimethyl 2h benzo[g]chromene 5,10 dione (6 methoxy alpha lapachone) 3,4 dihydro 7 hydroxy 2,2 dimethyl 2h benzo[g]chromene 5,6 dione (7 hydroxy beta lapachone) 3,4 dihydro 7 methoxy 2,2 dimethyl 2h benzo[h]chromene 5,6 dione (7 methoxy beta lapachone) 3,4 dihydro 8 hydroxy 2,2 dimethyl 2h benzo[h]chromene 5,6 dione (8 hydroxy beta lapachone) 3,4 dihydro 8 methoxy 2,2 dimethyl 2h benzo[g]chromene 5,10 dione (8 methoxy alpha lapachone) 3,4 dihydro 8 methoxy 2,2 dimethyl 2h benzo[h]chromene 5,6 dione (8 methoxy beta lapachone) 3,4 dihydro 9 hydroxy 2,2 dimethyl 2h benzo[g]chromene 5,10 dione (9 hydroxy alpha lapachone) 3,4,5,6 tetrahydro 2,2 dimethyl 5,6 dioxo 2h benzo[h]chromen 7 yl pivalate (7 pivaloyl beta lapachone) 7 hydroxy beta lapachone alpha lapachone antineoplastic agent benzene beta lapachone hydroxyl group isomerase inhibitor reactive oxygen metabolite unclassified drug antiproliferative activity article cell cycle cyclization cytotoxicity DNA damage drug synthesis protein expression tumor cell line Antineoplastic Agents Cell Cycle Cell Line, Tumor Cell Proliferation DNA Topoisomerases Humans Naphthoquinones Reactive Oxygen Species Topoisomerase Inhibitors Ríos-Luci, C. Bonifazi, E.L. León, L.G. Montero, J.C. Burton, G. Pandiella, A. Misico, R.I. Padrón, J.M. β-Lapachone analogs with enhanced antiproliferative activity |
| topic_facet |
β-Lapachone Antitumor agents Cell cycle Naphthoquinone Structure-activity relationships 2 hydroxy 5 methoxy 3 (3 methylbut 2 enyl)naphthalene 1,4 dione (5 methoxylapachol) 2 hydroxy 7 methoxynaphthalene 1,4 dione (2 hydroxy 7 methoxy 1,4 naphthoquinone 3 hydroxy 6 methoxy 2 (3 methylbut 2 en 1 yl)naphthalene 1,4 dione (7 methoxylapachol) 3,4 dihydro 10 hydroxy 2,2 dimethyl 2h benzo[g]chromene 5,6 dione (10 hydroxy beta lapachone) 3,4 dihydro 10 methoxy 2,2 dimethyl 2h benzo[g]chromene 5,6 dione (10 methoxy beta lapachone) 3,4 dihydro 6 hydroxy 2,2 dimethyl 2h benzo[g]chromene 5,10 dione (6 hydroxy alpha lapachone) 3,4 dihydro 6 hydroxy 2,2 dimethyl 2h benzo[g]chromene 5,10 dione (6 methoxy alpha lapachone) 3,4 dihydro 7 hydroxy 2,2 dimethyl 2h benzo[g]chromene 5,6 dione (7 hydroxy beta lapachone) 3,4 dihydro 7 methoxy 2,2 dimethyl 2h benzo[h]chromene 5,6 dione (7 methoxy beta lapachone) 3,4 dihydro 8 hydroxy 2,2 dimethyl 2h benzo[h]chromene 5,6 dione (8 hydroxy beta lapachone) 3,4 dihydro 8 methoxy 2,2 dimethyl 2h benzo[g]chromene 5,10 dione (8 methoxy alpha lapachone) 3,4 dihydro 8 methoxy 2,2 dimethyl 2h benzo[h]chromene 5,6 dione (8 methoxy beta lapachone) 3,4 dihydro 9 hydroxy 2,2 dimethyl 2h benzo[g]chromene 5,10 dione (9 hydroxy alpha lapachone) 3,4,5,6 tetrahydro 2,2 dimethyl 5,6 dioxo 2h benzo[h]chromen 7 yl pivalate (7 pivaloyl beta lapachone) 7 hydroxy beta lapachone alpha lapachone antineoplastic agent benzene beta lapachone hydroxyl group isomerase inhibitor reactive oxygen metabolite unclassified drug antiproliferative activity article cell cycle cyclization cytotoxicity DNA damage drug synthesis protein expression tumor cell line Antineoplastic Agents Cell Cycle Cell Line, Tumor Cell Proliferation DNA Topoisomerases Humans Naphthoquinones Reactive Oxygen Species Topoisomerase Inhibitors |
| description |
In this study, we describe the synthesis of a series of α- and β-lapachone containing hydroxyl or methoxyl groups on the benzene ring, by means of the selective acid promoted cyclization of the appropriate lapachol analog. The evaluation of the antiproliferative activity in human solid tumor cell lines provided 7-hydroxy-β-lapachone as lead with enhanced activity over the parent drug β-lapachone. Cell cycle studies, protein expression experiments, and reactive oxygen species analysis revealed that, similarly to β-lapachone, ROS formation and DNA damage are critical factors in the cellular toxicity of 7-hydroxy-β-lapachone. © 2012 Elsevier Masson SAS. All rights reserved. |
| format |
JOUR |
| author |
Ríos-Luci, C. Bonifazi, E.L. León, L.G. Montero, J.C. Burton, G. Pandiella, A. Misico, R.I. Padrón, J.M. |
| author_facet |
Ríos-Luci, C. Bonifazi, E.L. León, L.G. Montero, J.C. Burton, G. Pandiella, A. Misico, R.I. Padrón, J.M. |
| author_sort |
Ríos-Luci, C. |
| title |
β-Lapachone analogs with enhanced antiproliferative activity |
| title_short |
β-Lapachone analogs with enhanced antiproliferative activity |
| title_full |
β-Lapachone analogs with enhanced antiproliferative activity |
| title_fullStr |
β-Lapachone analogs with enhanced antiproliferative activity |
| title_full_unstemmed |
β-Lapachone analogs with enhanced antiproliferative activity |
| title_sort |
β-lapachone analogs with enhanced antiproliferative activity |
| url |
http://hdl.handle.net/20.500.12110/paper_02235234_v53_n_p264_RiosLuci |
| work_keys_str_mv |
AT rioslucic blapachoneanalogswithenhancedantiproliferativeactivity AT bonifaziel blapachoneanalogswithenhancedantiproliferativeactivity AT leonlg blapachoneanalogswithenhancedantiproliferativeactivity AT monterojc blapachoneanalogswithenhancedantiproliferativeactivity AT burtong blapachoneanalogswithenhancedantiproliferativeactivity AT pandiellaa blapachoneanalogswithenhancedantiproliferativeactivity AT misicori blapachoneanalogswithenhancedantiproliferativeactivity AT padronjm blapachoneanalogswithenhancedantiproliferativeactivity |
| _version_ |
1782030187575115776 |