ABSTRACT
Leishmaniasis is a neglected tropical disease and a public health concern in at least 98 countries, affecting mainly the poorest populations. Pharmaceuticals and chemotherapies available for leishmaniasis treatment have several limitations, which clearly justify the efforts to find new potential antileishmanial drugs. In this context, antiprotozoal activities toward different Leishmania species have been reported for hypervalent tellurium compounds, which motivated us to investigate, for the first time, the leishmanicidal properties of some nonhypervalent diaryl ditellurides. Thus, this work describes in vitro activity against Leishmania amazonensis and the cytotoxicities of diaryl ditellurides. Ditelluride LQ7 revealed a strong leishmanicidal activity on promastigotes and amastigotes at submicromolar levels (IC50 = 0.9 ± 0.1 and 0.5 ± 0.1 µmol L-1, respectively) and presented selectivity indexes greater than those of reference drug miltefosine. This preliminary study suggests that diaryl ditellurides may be promising scaffolds for the development of new agents for leishmaniasis treatment.
ABSTRACT
The use of antioxidants is the most effective means to protect the organism against cellular damage caused by oxidative stress. In this context, organotellurides have been described as promising antioxidant agents for decades. Herein, a series of N-functionalized organotellurium compounds has been tested as antioxidant and presented remarkable activities by three different in vitro chemical assays. They were able to reduce DPPH radical with IC50 values ranging from 5.08 to 19.20⯵gâ¯mL-1, and some of them also reduced ABTS+ radical and TPTZ-Fe3+ complex in ABTS+ and FRAP assays, respectively. Initial structure-activity relationship discloses that the nature of N-substituent strongly influenced both activity and cytotoxicity of the studied compounds. Furthermore, radical scavenging activities of N-functionalized organotellurides have been compared with those of their selenilated congeners, demonstrating that the presence of tellurium atom has an essential role in antioxidant activity.
Subject(s)
Free Radical Scavengers/chemistry , Organometallic Compounds/chemistry , Tellurium/chemistry , Animals , Benzothiazoles/chemistry , Biphenyl Compounds/chemistry , Drug Design , Fibroblasts/drug effects , Free Radical Scavengers/chemical synthesis , Free Radical Scavengers/toxicity , Mice , Molecular Structure , Organometallic Compounds/chemical synthesis , Organometallic Compounds/toxicity , Oxidation-Reduction , Picrates/chemistry , Structure-Activity Relationship , Sulfonic Acids/chemistryABSTRACT
The biological activity of tellurium compounds is closely related to the tellurium oxidation state or some of their structural features. Hypervalent dihalogenated organotelluranes 1-[butyl(dichloro)-λ4-tellanyl]-2-(methoxymethyl)benzene (1a) and 1-[butyl(dibromide)-λ4-tellanyl]-2-(methoxymethyl)benzene (1b) have been described as inhibitors of proteases (cysteine and threonine) and tyrosine phosphatases. However, poor attention has been given to their physicochemical properties. Here, a detailed investigation of the stability in water of these organotelluranes is reported using 125Te NMR analysis. Dihalogenated organotelluranes 1a and 1b were both stable in DMSO- d6 (from 25 to 75 °C), demonstrating their thermal stability. However, the addition of a phosphate buffer solution (pH 2-8) to 1a or 1b resulted in an immediate conversion to a new Te species, assumed to be the corresponding telluroxide. Similar behavior was observed in pure water, demonstrating the low chemical stability of these dihalogenated species in the presence of water. These results allow concluding that previous biological activity reported for dihalogenated organotelluranes 1a and 1b could be attributed to the corresponding derivatives from the reaction with water. In the same way as for AS-101, we demonstrated that organotelluranes 1a and 1b are not stable in aqueous solution. It suggests a proactive role of these organotelluranes in previously reported biological activity.
