RESUMO
Abstract INTRODUCTION: Aedes aegypti (L.) is the major vector of arboviruses that causes serious public health concerns in tropical and subtropical countries. METHODS: We examined the larvicidal activity of 1,2-diphenyldiselenide [(PhSe)2] and 1,2-bis(4-chlorophenyl) diselenide [(p-ClPhSe)2] and determine its toxicity to different non-target organisms. RESULTS: (PhSe)2 and (p-ClPhSe)2 killed Ae. aegypti L3 larvae with LC50/24h values of 65.63 µM (20.48 mg/L) and 355.19 µM (135.33 mg/L), respectively. (PhSe)2 was not toxic to the four model organisms. CONCLUSIONS: (PhSe)2 is a larvicidal compound with selective action against Ae. aegypti larvae. The mechanisms of action of (PhSe)2 under field conditions remain to be investigated.
Assuntos
Animais , Aedes , Inseticidas , Extratos Vegetais , Mosquitos Vetores , LarvaRESUMO
INTRODUCTION: Aedes aegypti (L.) is the major vector of arboviruses that causes serious public health concerns in tropical and subtropical countries. METHODS: We examined the larvicidal activity of 1,2-diphenyldiselenide [(PhSe)2] and 1,2-bis(4-chlorophenyl) diselenide [(p-ClPhSe)2] and determine its toxicity to different non-target organisms. RESULTS: (PhSe)2 and (p-ClPhSe)2 killed Ae. aegypti L3 larvae with LC50/24h values of 65.63 µM (20.48 mg/L) and 355.19 µM (135.33 mg/L), respectively. (PhSe)2 was not toxic to the four model organisms. CONCLUSIONS: (PhSe)2 is a larvicidal compound with selective action against Ae. aegypti larvae. The mechanisms of action of (PhSe)2 under field conditions remain to be investigated.
Assuntos
Aedes , Inseticidas , Animais , Larva , Mosquitos Vetores , Extratos VegetaisRESUMO
Organoselenium compounds and isoquinoline derivatives have their toxicity linked to induction of pro-oxidant situations. δ-Aminolevulinate dehydratase (δ-ALA-D) and Na+ , K+ -ATPase have sulfhydryl groups susceptible to oxidation. Thus, we investigated toxicological effects of 4-organoseleno-isoquinoline derivatives, cerebral monoamine oxidase B inhibitors, on rat cerebral δ-ALA-D and Na+ , K+ -ATPase activities and the involvement of sulfhydryl groups in vitro. Compounds substituted with fluoro (4-(4-fluorophenylseleno)-3-phenylisoquinoline), chloro (4-(4-chlorophenylseleno)-3-phenylisoquinoline) and trifluoro (4-(3-trifluoromethylphenylseleno)-3-phenylisoquinoline) at the selenium-bonded aromatic ring inhibited δ-ALA-D (IC50 values: 78.42, 92.27, 44.98 µM) and Na+ , K+ -ATPase (IC50 values: 41.36, 89.43, 50.66 µM) activities, possibly due to electronic effects induced by these groups. 3-Phenyl-4-(phenylseleno) isoquinoline (without substitution at the selenium-bonded aromatic ring) and 4-(4-methylphenylseleno)-3-phenylisoquinoline (with a methyl group substituted at the selenium-bonded aromatic ring) did not alter the activity of these enzymes. Dithiothreitol, a reducing agent, restored the enzymatic activities inhibited by 4-(4-fluorophenylseleno)-3-phenylisoquinoline, 4-(4-chlorophenylseleno)-3-phenylisoquinoline and 4-(3-trifluoromethylphenylseleno)-3-phenylisoquinoline, suggesting the involvement of sulfhydryl residues in this effect. However, the release of essential zinc seems not to be related to the δ-ALA-D inhibition by these compounds. According to these data, the effect of oral administration (300 mg/kg, intragastric) of 3-phenyl-4-(phenylseleno) isoquinoline on markers of systemic toxicity in Wistar rats was evaluated. None signs of toxicity was observed during or after treatment. This study suggests that the insertion of electron-withdrawing groups in the aromatic ring bonded to the selenium atom of isoquinolines tested increased its inhibitory effect on sulfhydryl enzymes in vitro. 3-Phenyl-4-(phenylseleno) isoquinoline, which has documented pharmacological properties, had no toxicological effects on the parameters evaluated in this study. J. Cell. Biochem. 118: 1144-1150, 2017. © 2016 Wiley Periodicals, Inc.
Assuntos
Isoquinolinas/toxicidade , Compostos Organosselênicos/toxicidade , Sintase do Porfobilinogênio/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Compostos de Sulfidrila/toxicidade , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Cloretos/farmacologia , Ditiotreitol/farmacologia , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Feminino , Isoquinolinas/química , Masculino , Compostos Organosselênicos/química , Sintase do Porfobilinogênio/antagonistas & inibidores , Ratos , Ratos Wistar , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Compostos de Sulfidrila/química , Testes de Toxicidade , Compostos de Zinco/farmacologiaRESUMO
Isoquinolines are formed endogenously as metabolites of neurotransmitters and are studied because they have structures similar to neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and selegiline, a selective inhibitor of MAO-B. This study investigated a possible in vitro inhibitory activity of new 4-organochalcogen-isoquinoline derivatives, containing sulfur 1, selenium 2 or tellurium 3 on MAO-A and B activities. Considering that the non-substituted selenoisoquinoline derivative 2 showed the best inhibitory profile (IC50 = 36.45 µM), new compounds were synthesized by adding substituents (methyl 2a, fluorine 2b, chloro 2c and trifluoromethyl 2d) to the aromatic ring bonded to the selenium atom of compound 2. All tested compounds were selective MAO-B inhibitors, although only the substituted isoquinoline derivative 2b showed IC50 lower than the concentration of 100 µM (IC50 = 82.41 µM). Compounds 2 and 2b were chosen to study the inhibitory profile. These compounds demonstrated reversible and mixed inhibition by decreasing apparent V (app) max and increasing apparent K (app) m, however the non-substituted compound 2 was a more potent inhibitor than the substituted compound 2b (K i = 7.07 and 16.30 µM). In conclusion, selenoisoquinolines 2 and 2b fit in the profile of third generation MAO inhibitors (selective and reversible), which are promising alternatives for treatment of emotional and neurodegenerative disorders.