RESUMO
We describe the in vitro activity of two natural isomeric ent-beyerene diterpenes, several derivatives and synthetic intermediates. Beyerenols 1 and 2 showed EC50 of 4.6⯱â¯9.4 and 5.3⯱â¯9.4⯵g/mL against amastigotes of L. (V) brazilensis, with SI of 5.1 and 7.7, respectively. Beyerenol 1 was synthesized from stevioside. In vivo experiments with bereyenols showed cure in 50% of hamsters infected with L. (V) brazilensis topically applied as Cream I (beyerenol 1, 0.81%, w/w) and Cream III (beyerenol 2, 1.96%, w/w). These results suggest that beyerenols are potential candidates for cutaneous leishmaniasis chemotherapy by topical application. In vitro assays of amastigotes of L. (V) brazilensis showed EC50 of 1.1⯱â¯0.1 and 1.3⯱â¯0.04⯵g/mL, with SI of 3.1 and 3.5 for hydrazone intermediates 10 and 11, respectively.
Assuntos
Diterpenos/uso terapêutico , Leishmaniose Cutânea/tratamento farmacológico , Tripanossomicidas/uso terapêutico , Animais , Linhagem Celular , Diterpenos/síntese química , Diterpenos/farmacologia , Diterpenos/toxicidade , Feminino , Humanos , Leishmania braziliensis/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Masculino , Mesocricetus , Tripanossomicidas/síntese química , Tripanossomicidas/farmacologia , Tripanossomicidas/toxicidadeRESUMO
A simple and easy reduction of trichloroacetyl compounds following the modification of Appel's reaction protocol, using triphenylphosphine and methanol, afforded the corresponding dichloroacetyl compounds, with the exception of trichloroacetylmorpholine, in yields of 80-98% under very mild experimental conditions. Likewise, when trichloromethyl heterocyclic compounds contain another reactive functional group, the reaction is highly chemoselective giving the dichloromethyl derivative.
RESUMO
Several natural and synthetic polypeptides possess important antimalarial activity. Shorter peptides with potent antimalarial activity have also been described, among them linear di-, tri-, tetra- and pentapeptides and their cyclic analogs. In an attempt to find dipeptides with antimalarial activities we show that linear and cyclic dipeptides, the latter known as diketopiperazines, still retain the fundamental core to preserve antimalarial activity. Thirteen linear dipeptides and ten diketopiperazines were investigated. Eight linear dipeptides showed IC(50) values between 2.78 and 7.07 µM, while eight diketopiperazines were also active with IC(50) values between 2.26 and 4.26 µM on Plasmodium berghei schizont cultures.
Assuntos
Antimaláricos/química , Dipeptídeos/química , Antimaláricos/síntese química , Antimaláricos/farmacologia , Cristalografia por Raios X , Dipeptídeos/síntese química , Dipeptídeos/farmacologia , Conformação Molecular , Peptídeos Cíclicos/síntese química , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Plasmodium berghei/efeitos dos fármacosRESUMO
Addition of organocuprates, generated in situ using an excess of a 1:2 mixture of CuI·DMS and Grignard reagent, to N-enoyl oxazolidinethiones in the presence of excess TMSI gave preferentially the anti diastereomer where the addition took place when the conformation of the substrate was syn-s-cis. The reaction was investigated with indene-based and three different phenyl glycine derived oxazolidinethiones.