RESUMO
The synthesis and in-vitro antiprotozoal evaluation of novel N(4)-(benzyl)spermidyl-linked bis(1,3,5-thiadiazinane-2-thione) (bis-THTT) derivatives from N(4)-(benzyl)spermidine is disclosed. Several of the new bis-THTT have in-vitro activities against L. donovani and T. cruzi that are comparable or superior to those of currently employed protozoocidal agents.
Assuntos
Antiprotozoários/síntese química , Tionas/síntese química , Animais , Antiprotozoários/farmacologia , Avaliação Pré-Clínica de Medicamentos , Leishmania donovani/efeitos dos fármacos , Espermidina/química , Relação Estrutura-Atividade , Tionas/farmacologia , Trypanosoma cruzi/efeitos dos fármacosRESUMO
Based on experimental evidence and DFT studies, a probable cyclization route to 1,3,5-thiadiazinanes-2-thiones in aqueous medium is proposed. Experimental facts suggest the formation of a {[hydroxymethyl (substituted) carbamothioyl] sulfanyl}methanol intermediate via reaction of dithiocarbamate (DTC) and formaldehyde. Nucleophilic addition of glycine to this intermediate generates an adduct that undergoes intramolecular heterocyclization via an S(N)2 reaction. Computational calculations predict an active role of water in the reaction mechanism that promotes intramolecular cyclization.
Assuntos
Simulação por Computador , Tionas/síntese química , Água/química , Ciclização , Glicina/química , Modelos Moleculares , Termodinâmica , Tionas/químicaRESUMO
Se evaluó la capacidad infectiva de promastigotes de Leishmania amazonensis al ser tratados con una serie de 10 derivados de la tiadiazina. Los parásitos fueron incubados durante 24 h con 1 o 0,1 mg/mL de cada compuesto y posteriormente, se infectaron macrófagos peritoneales de ratones BALB/c en cultivos. Todos los compuestos causaron una reducción de la capacidad infectiva de los parásitos mayor que 50 %. El producto T1O fue el que causó un mayor efecto, disminuyendo la infección en 92,8 % de infección.
The infective capacity of Leishmania amazonensis promastigotes was evaluated after they were treated with a series of 10 thiadiazine derivatives. The parasites were incubated for 24 hours with 1 or 0,1 mg/ml of each compound and then, peritoneal macrophages from BALB/c mice were infected in cultures. All the compounds managed to reduce the infective capacity of parasites by more than 50%. T10 product exhibited the highest effect since it reduced infection by 92,8%.
RESUMO
Current therapy for leishmaniasis is not satisfactory. We describe the in vitro antiproliferative effects of new thiadiazine derivatives against Leishmania amazonensis. The compounds were found to be active against the amastigote form of the parasite, inhibiting parasite growing, from 10 to 89%, at a concentration of 100 ng/ml. This activity suggests that thiadiazine derivatives could be considered as potential antileishmanial compounds.
Assuntos
Antiprotozoários/farmacologia , Leishmania braziliensis/efeitos dos fármacos , Tiadiazinas/farmacologia , Animais , Concentração Inibidora 50 , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade ParasitáriaRESUMO
Current therapy for leishmaniasis is not satisfactory. We describe the in vitro antiproliferative effects of new thiadiazine derivatives against Leishmania amazonensis. The compounds were found to be active against the amastigote form of the parasite, inhibiting parasite growing, from 10 to 89 percent, at a concentration of 100 ng/ml. This activity suggests that thiadiazine derivatives could be considered as potential antileishmanial compounds.