Synthesis, Mechanism Elucidation and Biological Insights of Tellurium(IV)-Containing Heterocycles.

Inspired by the synthetic and biological potential of organotellurium substances, a series of five- and six-membered ring organotelluranes containing a Te-O bond were synthesized and characterized. Theoretical calculations elucidated the mechanism for the oxidation-cyclization processes involved in the formation of the heterocycles, consistent with chlorine transfer to hydroxy telluride, followed by a cyclization step with simultaneous formation of the new Te-O bond and deprotonation of the OH group. Moreover, theoretical calculations also indicated anti-diastereoisomers to be major products for two chirality center-containing compounds. Antileishmanial assays against Leishmania amazonensis promastigotes disclosed 1,2λ4 -oxatellurane LQ50 (IC50 =4.1±1.0; SI=12), 1,2λ4 -oxatellurolane LQ04 (IC50 =7.0±1.3; SI=7) and 1,2λ4 -benzoxatellurole LQ56 (IC50 =5.7±0.3; SI=6) as more powerful and more selective compounds than the reference, being up to four times more active. A stability study supported by 125 Te NMR analyses showed that these heterocycles do not suffer structural modifications in aqueous-organic media or at temperatures up to 65 °C.

Diacetal Ditellurides as Highly Active and Selective Antiparasitic Agents toward Leishmania amazonensis.

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.