ABSTRACT
BACKGROUND: Trypanosomiasis and leishmaniasis cause severe infections in humans and domestic animals in the tropics. Although typical diseases in Latin America, globalization and the migration of infected people has spread these diseases to countries in North America, Asia and Europe. Currently available drugs are not effective in the chronic phase, as well as cause side effects and develop resistance. RESULTS: Among the chemical groups studied as potential anti-T. cruzi and anti-Leishmania are the thio-and semicarbazones, which are easy to obtain, possess structural versatility and can sequester metal. In this article, we present an overview of thio-and semicarbazones associated with heterocycles, indanones, and styryl and aryl skeletons, including their metal complexes with antimony, platinum, palladium, copper, ruthenium, rhenium, manganese and vanadium. CONCLUSION: Because of the efficiency and selectivity that some of these derivatives have shown, it can be concluded that thio-and semicarbazones constitute promising chemical scaffolds in the search for new anti-parasitic agents.
Subject(s)
Chagas Disease/drug therapy , Drug Discovery/methods , Leishmaniasis/drug therapy , Semicarbazones/pharmacology , Sulfur/chemistry , Semicarbazones/chemistry , Semicarbazones/therapeutic useABSTRACT
Herein, we describe a new approach towards the synthesis of selenosemicarbazones. The reaction involves an O-Se exchange of semicarbazones using Ishihara reagent. Eleven selenosemicarbazones were prepared using this methodology, with low to moderate yields. Among the prepared compounds the m-bromo phenyl methyl derivative 1b was selected to be evaluated in vivo, in a murine model of acute Chagas' disease. Compound 1b 10 mg/kg bw/day reduced 50% of parasitaemia profile compared with the control group, but was less effective than Benznidazole (50 mg/kg bw/day reduced 90%) and toxic. These studies are important to guide future Chagas drug design.
Subject(s)
Chagas Disease/drug therapy , Organoselenium Compounds/chemical synthesis , Organoselenium Compounds/therapeutic use , Semicarbazones/chemical synthesis , Semicarbazones/therapeutic use , Trypanocidal Agents/chemical synthesis , Trypanocidal Agents/therapeutic use , Acute Disease , Animals , Chemistry Techniques, Synthetic , Drug Design , Male , Mice , Mice, Inbred BALB C , Organoselenium Compounds/chemistry , Semicarbazones/chemistry , Trypanocidal Agents/chemistry , Trypanosoma cruzi/drug effectsABSTRACT
Seventeen semicarbazone and thiosemicarbazone derivatives were prepared and tested in vitro against a chloroquine resistant strain of Plasmodium falciparum (W2) to evaluate their antiplasmodial potential. Three thiosemicarbazones were found to be active against the parasite and non-toxic to human peripheral blood mononuclear cells (PBMC). Among these, compound 5b presented the lowest IC50 value against P. falciparum (7.2 microM) and was the least toxic in the PBMC proliferation assay (IC50=73.5 microM). It was selected for in vivo tests on mice infected with Plasmodium berghei (strain NK-65). The thiosemicarbazone 5b was able to reduce the parasitaemia by 61% at 20 mg/kg on day 7 after infection without any sign of toxicity to the animals. In comparison, the standard drug chloroquine at 15 mg/kg showed a reduction around 95%. These in vitro and in vivo results make 5b an interesting lead for further development.
Subject(s)
Semicarbazones/chemical synthesis , Semicarbazones/pharmacology , Thiosemicarbazones/chemical synthesis , Thiosemicarbazones/pharmacology , Animals , Cell Proliferation/drug effects , Humans , Lymphocytes/cytology , Lymphocytes/drug effects , Malaria/drug therapy , Mice , Plasmodium falciparum/drug effects , Semicarbazones/chemistry , Semicarbazones/therapeutic use , Thiosemicarbazones/chemistry , Thiosemicarbazones/therapeutic useABSTRACT
The convulsions of approximately 25% of epileptics are inadequately controlled by currently available medication; therefore the preparation of new antiepileptic drugs is of great interest. Aryl semicarbazones can be considered a new class of compounds presenting anticonvulsant activity. In addition, they can be orally administered and are more active as anticonvulsants than mephenytoin or phenobarbital. However, one disadvantage of these compounds is their low water solubility. As a strategy to circumvent this problem, a 1:1 inclusion compound of benzaldehyde semicarbazone (BS) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was prepared and characterized. The anticonvulsant activities of the free semicarbazone and of the inclusion compound were evaluated in rats using the maximum electroshock and audiogenic seizures screenings. In both tests the minimum dose of compound necessary to produce activity decreases from 100mg/kg for the free semicarbazone to 35 mg/kg for the inclusion compound, indicating a significant increase in the bio-availability of the drug.