Antimalarial activity of new acridinone derivatives
Malaria is one of the major threats concerning world public health. Resistance to the current antimalarial drugs has led to searches for new antimalarial compounds. Acridinone derivatives have recently demonstrated to be active against malaria parasite. We focused our attention on synthesized new ac...
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todo:paper_07533322_v65_n3_p210_FernandezCalienes2023-10-03T15:39:37Z Antimalarial activity of new acridinone derivatives Fernández-Calienes, A. Pellón, R. Docampo, M. Fascio, M. D'Accorso, N. Maes, L. Mendiola, J. Monzote, L. Gille, L. Rojas, L. Acridinone Antimalarial activity Plasmodium falciparum 10 (1,2 propadienyl) 9 (10h) acridinone 10 (3 methyl 2 butenyl) 9 (10h) acridinone 10 allyl 9 (10h) acridinone antimalarial agent atovaquone beta hematin chloroquine heme derivative stigmatellin unclassified drug animal cell antimalarial activity article controlled study cow cytotoxicity drug selectivity heart muscle cell human human cell IC 50 nonhuman Plasmodium falciparum priority journal spectrophotometry yeast Acridines Animals Antimalarials Cattle Cell Line Drug Resistance, Microbial Hemeproteins Humans Malaria Plasmodium falciparum Yeasts Malaria is one of the major threats concerning world public health. Resistance to the current antimalarial drugs has led to searches for new antimalarial compounds. Acridinone derivatives have recently demonstrated to be active against malaria parasite. We focused our attention on synthesized new acridinone derivatives, some of them resulting with high antiviral and trypanocidal activity. In this study new derivatives of 10-alyl-, 10-(3-methyl-2-butenyl)- and 10-(1,2-propadienyl)-9(10H)-acridinone were evaluated for their antimalarial activity against Plasmodium falciparum. To assess the selectivity, cytotoxicity was assessed in parallel against human MRC-5 cells. Inhibition of β-hematin formation was determined using a spectrophotometric assay. Mitochondrial bc 1 complexes were isolated from yeast and bovine heart cells to test acridinone inhibitory activity. This study resulted in the identification of three compounds with submicromolar efficacy against P. falciparum and without cytotoxic effects on human cellular line. One compound, IIa (1-fluoro-10-(3-methyl-2-butenyl)-9(10H)-acridinone), can be classified as hit for antimalarial drug development exhibiting IC 50 less than 0.2μg/mL with SI greater than 100. In molecular tests, no relevant inhibitory activity was obtained for our compounds. The mechanism of acridinones antimalarial action remains unclear. © 2011 Elsevier Masson SAS. Fil:Fascio, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:D'Accorso, N. 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_07533322_v65_n3_p210_FernandezCalienes |
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Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Acridinone Antimalarial activity Plasmodium falciparum 10 (1,2 propadienyl) 9 (10h) acridinone 10 (3 methyl 2 butenyl) 9 (10h) acridinone 10 allyl 9 (10h) acridinone antimalarial agent atovaquone beta hematin chloroquine heme derivative stigmatellin unclassified drug animal cell antimalarial activity article controlled study cow cytotoxicity drug selectivity heart muscle cell human human cell IC 50 nonhuman Plasmodium falciparum priority journal spectrophotometry yeast Acridines Animals Antimalarials Cattle Cell Line Drug Resistance, Microbial Hemeproteins Humans Malaria Plasmodium falciparum Yeasts |
| spellingShingle |
Acridinone Antimalarial activity Plasmodium falciparum 10 (1,2 propadienyl) 9 (10h) acridinone 10 (3 methyl 2 butenyl) 9 (10h) acridinone 10 allyl 9 (10h) acridinone antimalarial agent atovaquone beta hematin chloroquine heme derivative stigmatellin unclassified drug animal cell antimalarial activity article controlled study cow cytotoxicity drug selectivity heart muscle cell human human cell IC 50 nonhuman Plasmodium falciparum priority journal spectrophotometry yeast Acridines Animals Antimalarials Cattle Cell Line Drug Resistance, Microbial Hemeproteins Humans Malaria Plasmodium falciparum Yeasts Fernández-Calienes, A. Pellón, R. Docampo, M. Fascio, M. D'Accorso, N. Maes, L. Mendiola, J. Monzote, L. Gille, L. Rojas, L. Antimalarial activity of new acridinone derivatives |
| topic_facet |
Acridinone Antimalarial activity Plasmodium falciparum 10 (1,2 propadienyl) 9 (10h) acridinone 10 (3 methyl 2 butenyl) 9 (10h) acridinone 10 allyl 9 (10h) acridinone antimalarial agent atovaquone beta hematin chloroquine heme derivative stigmatellin unclassified drug animal cell antimalarial activity article controlled study cow cytotoxicity drug selectivity heart muscle cell human human cell IC 50 nonhuman Plasmodium falciparum priority journal spectrophotometry yeast Acridines Animals Antimalarials Cattle Cell Line Drug Resistance, Microbial Hemeproteins Humans Malaria Plasmodium falciparum Yeasts |
| description |
Malaria is one of the major threats concerning world public health. Resistance to the current antimalarial drugs has led to searches for new antimalarial compounds. Acridinone derivatives have recently demonstrated to be active against malaria parasite. We focused our attention on synthesized new acridinone derivatives, some of them resulting with high antiviral and trypanocidal activity. In this study new derivatives of 10-alyl-, 10-(3-methyl-2-butenyl)- and 10-(1,2-propadienyl)-9(10H)-acridinone were evaluated for their antimalarial activity against Plasmodium falciparum. To assess the selectivity, cytotoxicity was assessed in parallel against human MRC-5 cells. Inhibition of β-hematin formation was determined using a spectrophotometric assay. Mitochondrial bc 1 complexes were isolated from yeast and bovine heart cells to test acridinone inhibitory activity. This study resulted in the identification of three compounds with submicromolar efficacy against P. falciparum and without cytotoxic effects on human cellular line. One compound, IIa (1-fluoro-10-(3-methyl-2-butenyl)-9(10H)-acridinone), can be classified as hit for antimalarial drug development exhibiting IC 50 less than 0.2μg/mL with SI greater than 100. In molecular tests, no relevant inhibitory activity was obtained for our compounds. The mechanism of acridinones antimalarial action remains unclear. © 2011 Elsevier Masson SAS. |
| format |
JOUR |
| author |
Fernández-Calienes, A. Pellón, R. Docampo, M. Fascio, M. D'Accorso, N. Maes, L. Mendiola, J. Monzote, L. Gille, L. Rojas, L. |
| author_facet |
Fernández-Calienes, A. Pellón, R. Docampo, M. Fascio, M. D'Accorso, N. Maes, L. Mendiola, J. Monzote, L. Gille, L. Rojas, L. |
| author_sort |
Fernández-Calienes, A. |
| title |
Antimalarial activity of new acridinone derivatives |
| title_short |
Antimalarial activity of new acridinone derivatives |
| title_full |
Antimalarial activity of new acridinone derivatives |
| title_fullStr |
Antimalarial activity of new acridinone derivatives |
| title_full_unstemmed |
Antimalarial activity of new acridinone derivatives |
| title_sort |
antimalarial activity of new acridinone derivatives |
| url |
http://hdl.handle.net/20.500.12110/paper_07533322_v65_n3_p210_FernandezCalienes |
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