Biological evaluation of some selected cyclic imides: mitochondrial effects and in vitro cytotoxicity.
Cyclic imides such as succinimides, maleimides, glutarimides, phthalimides and their derivatives contain an imide ring and a general structure -CO-N(R)-CO- that confers hydrophobicity and neutral characteristic. A diversity of biological activities and pharmaceutical uses have been attributed to them, such as antibacterial, antifungal, antinociceptive, anticonvulsant, antitumor. In spite of these activities, much of their action mechanisms at molecular and cellular levels remain to be elucidated. We now show the effects of several related cyclic imides: maleimides (S2, S2.1, S2.2, S3), glutarimides (S4, S5, S6), 4-aminoantipyrine derivatives (L1, F1, AL1, F1.14, F1.2) and sulfonated succinimides (RO1, FA, FE, FD, MC, DMC) on isolated rat liver mitochondria, B16-F10 melanoma cell line, peritoneal macrophages and different bacterial streams. The effects on mitochondrial respiratory parameters, cell viability and antibacterial activity were also evaluated. The results indicated that S3, S5 and S6 caused an increased oxygen consumption in the presence of ADP (state III) or its absence (state IV), while all other compounds decreased those parameters at different degrees of inhibition. All the compounds decreased the respiratory control coefficient (RCC). Loss of cell viability of peritoneal macrophages and the B16-F10 cell line was observed, L1 and S2.1 being more effective. S1, S2, S3, L1 and F1 compounds showed antibacterial activity at experimental concentrations.
Prado
Silvia Regina Tozato
SR
Department of Biochemistry and Molecular Biology, Federal University of Parana, Curitiba, Paraná, Brazil.
Cechinel-Filho
Valdir
V
Campos-Buzzi
Fátima
F
Corrêa
Rogério
R
Cadena
Silvia Maria Correia Suter
SM
de Oliveira
Maria Benigna Martinelli
MB
D000244:Adenosine Diphosphate / Q000378:metabolism; D000675:Ampyrone / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D007094:Imides / Q000737:chemistry* / Q000633:toxicity*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000473:pathology; D008301:Maleimides / Q000737:chemistry / Q000494:pharmacology; D008546:Melanoma, Experimental; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000473:pathology; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D013329:Structure-Activity Relationship
D000890:Anti-Infective Agents; D007094:Imides; D008301:Maleimides; D000675:Ampyrone; D000244:Adenosine Diphosphate