Vinylic telluride derivatives as promising pharmacological compounds with low toxicity.
The aim of the present study was to evaluate pharmacological and toxicological properties of (Z)-2-(methylthio)-1-(butyltelluro)-1-phenylethene 1a, (Z)-1-(4-methylphenylsulfonyl)-2-(phenyltelluro)-2-phenylethene 1b, (Z)-2-(butyltelluro)-1-(benzylthio)-1-heptene 1c and (Z)-2-(phenylthio)-1-(butyltelluro)-1-phenylethene 1d. In vitro, vinylic telluride derivatives 1a, 1d and 1c were more effective in reducing lipid peroxidation than compound 1b. The maximal inhibitory effect of vinylic telluride derivatives on lipid peroxidation was in the following order: 1a = 1d > 1c > 1b. Compound 1b was more potent in inhibiting delta-ALA-D activity (delta-aminolevulinate dehydratase) than compounds 1c and 1d. Based on the in vitro properties presented by compounds 1a (an antioxidant) and 1b (a pro-oxidant), toxicological parameters were assessed in vivo and ex vivo in rats. Calculated LD50 of compounds 1a and 1b, administered by oral route, were 20.5 and 1.44 micromol kg(-1), respectively. Compound 1b induced behavioral alterations in the open field test. Renal and spleenic delta-ALA-D activities were inhibited in rats treated orally with compound 1a. Compound 1b stimulated delta-ALA-D activity in liver and spleen of rats. Rats treated with compound 1b had increased hepatic, renal and spleenic lipid peroxidation. Renal and hepatic markers were not altered when compounds 1a and 1b were administered to rats at doses of around LD50, while compound 1a at high doses changed aspartate aminotransferase activity and urea levels. Based on in vitro results, this study demonstrated that compounds 1a and 1d are promising antioxidant compounds. Ex vivo data reinforce compound 1a as a promising drug for more detailed pharmacological studies.
Borges
V C
VC
Departamento de Química, Centro de Ciencias Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil.
Savegnago
L
L
Pinton
S
S
Jesse
C R
CR
Alves
D
D
Nogueira
C W
CW
D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000633:toxicity*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009929:Organ Size / Q000187:drug effects; D009942:Organometallic Compounds / Q000633:toxicity*; D000623:Porphobilinogen Synthase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013691:Tellurium / Q000633:toxicity*
D000975:Antioxidants; D009942:Organometallic Compounds; D003546:Cysteine Endopeptidases; D000623:Porphobilinogen Synthase; D013691:Tellurium