Selective cytotoxicity and apoptosis induction in glioma cell lines by 5-oxygenated-6,7-methylenedioxycoumarins from Pterocaulon species.
The coumarins 5-methoxy-6,7-methylenedioxycoumarin 1 5-(3-methyl-2-butenyloxy)-6,7-methylenedioxycoumarin 2 and 5-(2,3-dihydroxy-3-methylbutyloxy)-6,7-methylenedioxycoumarin 3 isolated from Pterocaulon species showed significant cytotoxicity against two glioma cells lines. Compound 1 presented IC(50) values of 34.6 μM and 31.6 μM against human (U138-MG) and rat (C6) glioma cells, respectively, and this compound was at least two times more potent than compounds 2 and 3. This result could be explained by the planar conformation adopted by 1 through a non-classical hydrogen bond between a hydrogen of the methoxy and the oxygen of the methylenedioxy groups. Another important finding was that the cytotoxic effect induced by 1 in glioma cells was not observed in organotypic cultures, indicating a selective cytotoxicity for tumor cells.
Programa de Pós Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul., Av. Ipiranga 2752, CEP 90610-000, Porto Alegre/RS, Brazil. 00121940@ufrgs.br
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Vianna
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Hamerski
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Figueiró
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Bernardi
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Visentin
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Pires
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Teixeira
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Salbego
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Eifler-Lima
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Battastini
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von Poser
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Pinto
D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D019659:Asteraceae / Q000737:chemistry*; D052117:Benzodioxoles / Q000302:isolation & purification* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016543:Central Nervous System Neoplasms / Q000188:drug therapy / Q000473:pathology; D003374:Coumarins / Q000302:isolation & purification* / Q000494:pharmacology; D003603:Cytotoxins / Q000302:isolation & purification* / Q000494:pharmacology; D005910:Glioma / Q000188:drug therapy / Q000473:pathology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D006801:Humans; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D008297:Male; D009928:Organ Specificity; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D046509:Tissue Culture Techniques
C580933:5-(2,3-dihydroxy-3-methylbutyloxy)-6,7-methylenedioxycoumarin; C580932:5-(3-methyl-2-butenyloxy)-6,7-methylenedioxycoumarin; C580931:5-methoxy-6,7-methylenedioxycoumarin; D000970:Antineoplastic Agents; D052117:Benzodioxoles; D003374:Coumarins; D003603:Cytotoxins