In vitro Activities of Thiadiazine Derivatives against Leishmania amazonensis

Abstract

Ten thiadiazine derivatives were tested in vitro for antiparasitic effects against both extracellular promastigotes and intracellular amastigotes of Leishmania amazonensis. The results showed that the evaluated compounds exhibited a strong antiproliferative activity on all developmental stages of the parasite. The minimal inhibitory concentration and the 50 % effective concentration values against the promastigote were 2.1-5.1 microg/ml and 0.6-1.8 microg/ml, respectively. The tested compounds caused an irreversible inhibition of the promastigote growth either after 1 h of treatment with 10 microg/ml or after 24 h with 1 microg/ml. Also, the thiadiazine derivatives were active against amastigotes producing between 12 and 89 % of reduction of infection at 100 ng/ml. However, the compounds exhibited high toxicity and provoked inhibition of the phagocytosis in the murine host cell.

Thiadiazine Derivatives as Antiprotozoal New Drugs

“…These results confirmed that the THTT represent a group of compounds with significant in vitro activity against L. amazonensis and suggested that some of them could be considered for further study as new therapeuthic alternatives [32,33]. …”

“…8 ) were tested in vitro for antiparasitic effects against both extracellular promastigotes and intracellular amastigotes of Leishmania amazonensis [32,33] . 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 µg/mL.…”

“…10 ). However, the compounds exhibited high toxicity and produced inhibition of the phagocytosis in the murine host cell [33]. The mono–THTT tested exhibited a strong activity against L. amazonensis at low concentrations.…”

Liquid phase organic synthesis of 3,5-disubstituted 1,3,5-thiadiazinane-2-thione derivatives on polyethylene glycol (PEG) support

“…17 The antiparasitic properties of some 5-carboxyalkyl-3-furfuryl-1,3,5-thiadiazinane-2-thione against both extracellular promastigotes and intracellular amastigotes of Leishmania amazonensis have also been reported. 18,19 The results showed that the evaluated compounds exhibited a strong antiproliferative activity on all developmental stages of the parasite. Following our ongoing project to develop new antiparasitic agents using the THTT ring as the central core, we have also reported the synthesis and biological activity of bis(1,3,5-thiadiazinane-2-thiones) derivatives where the two thiadiazinane rings are linked by an alkyl chain 20 or a linear polyamine moiety.…”

“…21 Taking to account the interaction mechanism suggested for this heterocycle, the incorporation of two THTT moiety in the same structure must increase the activity of these derivatives as antiparasitic agents. 22 We have previously demonstrated the feasibility of the synthesis of thiadiazinane-2-thiones in solution [14][15][16][18][19][20][21] by reaction of the appropriate amine with carbon disulfide and potassium hydroxide, to give the dithiocarbamate potassium salt, which is not isolated, followed by cyclocondensation with formaldehyde and the selected amino acids or pseudopeptides able to provide the nitrogen atom at the N-5 position of the thiadiazinane ring. Based on experimental evidence and DFT studies, a probable cyclization route to 1,3,5-thiadiazinane-2-thiones in aqueous medium was proposed.…”