Synthesis and Antiprotozoan Properties of New 3,5-Disubstituted-tetrahydro-2H-1,3,5-thiadiazine- 2-thione Derivatives (original) (raw)
Related papers
New thiadiazine derivatives with activity against trypanosoma cruzi amastigotes
Folia Parasitologica, 2013
The cytotoxicity of 18 new 1,2,6-thiadiazin-3,5-dione 1,1-dioxides was evaluated. This group of products was previously assayed against epimastigotes of Trypanosoma cruzi and some of them showed a high antiprotozoal activity. Thereafter 13 compounds with a high anti-epimastigote activity and low cytotoxicity were selected to be assayed against amastigotes. Some of the products showed the same or even lower cytotoxicity than nifurtimox and benznidazole, but most of them were very toxic for macrophages at 100 µg/ml. Only one of the compounds had an anti-amastigote activity similar to that of reference drugs at 10 µg/ml, but unfortunately this disappeared at lower concentrations.
Memorias Do Instituto Oswaldo Cruz, 2002
Cytotoxicity assays of 24 new 3,5-disubstituted-tetrahydro-2H-1,3,5-thiadiazin-2-thione derivatives were performed. The 17 compounds with higher anti-epimastigote activity and lower cytotoxicity were, thereafter, screened against amastigote of Trypanosoma cruzi. Out of these 17 derivatives S-2d was selected to be assayed in vivo, because of its remarkable trypanocidal properties. To determine toxicity against J774 macrophages, a method based on quantification of cell damage, after 24 h, was used. Cell respiration, an indicator of cell viability, was assessed by the reduction of MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] to formazan. Antiamastigote activity was estimated after 48 h by microscopic counts of May Grünwald-Giemsa-stained monolayers. Nifurtimox and benznidazole were used as reference drugs. For the in vivo experiences, mice were infected with 10 4 blood trypomastigotes and then treated during 15 days with S-2d or nifurtimox by oral route. All of the compounds were highly toxic at 100 µg/ml for macrophages and a few of them maintained this cytotoxicity even at 10 µg/ml. Of the derivatives assayed against amastigotes 3k and S-2d showed an interesting activity, that was held even at 1µg/ ml. It is demonstrated that the high anti-epimastigote activity previously reported is mainly due to the non-specific toxicity of these compounds. In vivo assays assessed a reduction of parasitemia after administration of S-2d to infected mice.
Frontiers in Drug, Chemistry and Clinical Research, 2019
Chagas disease is a serious public health problem in Brazil and world. Caused by the protozoan Trypanosoma cruzi, it is estimated 6-7 million people infected worldwide. The only drug used to treatment is Benzonidazole, but this drug is only effective in the acute phase of the disease. This paper reports the synthesis and the anti-Trypanosoma cruzi activity of 4-thiazolidinone and 1,3-thiazole derivatives based in thiosemicarbazones previously described as potent trypanocidal agent, planned through the bioisosterism strategy. Therefore, the synthesis of 28 aryl-4-thiazolidinones (2a-r and 3a-j) was achieved, which aryl ring possesses halogens atoms in meta and para positions, and the heterocyclic system had lipophilic substituents. These compounds were thus evaluated as anti-T. cruzi agents against epimastigote, trypomastigote and amastigote forms of T. cruzi. Compounds were also tested its toxicity in L929 fibroblasts. In view to investigate a bioisosteric relationship between 1,3-thiazoles and 4-thiazolidinones, eighteen 1,3-thiazoles derived from trifluoromethyl thiosemicarbazone (4a-r) were also tested in the same model. It was possible to show that between the 46 tested compounds, those that possess a bromine (2a-r) atom showed better activity compared to compounds substituted by a trifluoromethyl group (3a-j) and to 1,3-thiazole derivatives (4a-r), which were inactive. In general, the 2a-r series showed low toxic profile in the cell line tested. Besides, compound 2h was the most active of then all when compared to the standard Benznidazole.
International Journal of Biological and Chemical Sciences, 2011
Six 1,3,4-thiadiazolines derivatives were synthesized by cyclization of thiosemicarbazones under acetylating condition with yields going from 27 to 94%. The products purity was confirmed by LC/MS (Mass Spectrometry Coupled with High-Performance Liquid Chromatography) and they were characterized using spectrometry IR, NMR 1 H and 13 C (Nuclear Magnetic Resonance). These compounds were then tested in vitro on Trypanosoma brucei brucei according to the "LILIT, Alamar Blue" method to estimate their trypanocidal activity. 1,3,4-thiadiazoline 6 (IC 50 = 38,79 µM) was the most active of all compounds.
Archiv der Pharmazie, 2008
The purpose of this study is based upon design and synthesis of a new series of flexible molecules of 3,4,5,6-tetrahydro-2H-1,3,5-thiadiazine-2-thione (THTT) derivatives depending upon incorporation of 2-aminoethanol as a part of the polar moiety in this nucleus. Thirteen derivatives of 3-substituted-5-(2-hydroxyethyl)-3,4,5,6-tetrahydro-2H-1,3,5-thiadiazine-2-thione were synthesized by reaction of the appropriate alkyl, cycloalkyl, aralkyl amine, or glycine with carbon disulphide, formaldehyde, and 2-aminoethanol. The structures of the target compounds were elucidated using spectral methods as well as elemental analyses. A mass-spectrometry study was carried out on representatives of the synthesized derivatives. The title compounds were tested for their antibacterial activity in vitro against some gram positive and gram negative bacteria. The in-vitro antifungal activity was tested against dermatophytic, saprophytic, phytopathogenic, and antagonistic fungi. In most cases, the newly synthesized compounds 4 -16 exhibited a considerable inhibitory effect on the growth of some of the tested organisms in comparison to that of ampicillin or muconazole as reference drugs. Moreover, the results indicated that the polar hydroxyethyl group at the N5-and the lipophilic one at the N3-positions are essential for the antimicrobial activity of the tested compounds.
Thiadiazine Derivatives as Antiprotozoal New Drugs
Open Medicinal …, 2011
The 3,5-disubstituted tetrahydro-2H-1,3,5-thiadiazine-2-thione scaffold have found many applications in recent years. This review is aimed at highlighting the most important aspects about these compounds: synthesis, spectroscopic characterization and antiprotozoan activities. How the chemical nature of N-substituents influences the overall activity / cytotoxicity profile will also be discussed.
2017
were screened for their antibacterial and antifungal activities against some selected pathogenic organisms like Escherichia coli, Proteus vulgaris, Staphylococcus aureus, Salmonella typhimurium, Klebsiella pneumonie, Psudomonas aeruginosa, Aspergillus Niger and Candida albicance. These compounds show appreciable activity towards these microorganisms. The identities of these newly synthesized-1,3,5-thiadiazines have been established on the basis of elemental analysis, IR, 1 HNMR and MASS spectral studies. The literature survey reveals that the heterocyclic compounds having 1, 3, 5-thiadiazines nucleus enhanced pharmaceutical, medicinal, agricultural and industrial values. The high synthetic versatility exhibited by the isothiocyanate moiety has allowed its use as a building block in the preparation of a variety of derivatives. In carbohydrates, the strong electrophilicity shown by isothiocyanates, together with the possibility of undergoing cyclization reaction has made it possible t...
Synthesis and antimicrobial activity of novel 1,3,4-thiadiazine derivatives
2013
Compound (1) was treated with phenacyl bromide to yield compound (3), which was brominated to yield compound (4) and Further condensed with piperazine ester to obtained compound (6). Compound (6) was treated with hydrazine hydrate to obtained compound (7), which on further treatment with aromatic aldehydes which yielded corresponding Schiff base compound (8). Compound (8) in acidic medium undergoes cyclization to yield respective novels thiadiazine derivatives(9). The structures of the newly synthesized compounds were confirmed by IR, 1H NMR and mass spectroscopic analysis.
Twelve new 3-(isobutyl)-5-substituted-tetrahydro-2H-1,3,5-thiadiaz-ine-2-thiones were synthesized by the reaction of isobutylamine with carbon disulfide and potassium hydroxide, followed by formaldehyde and appropriate alkyl, cycloalkyl aralkyl amines, amino acid, and INH. Their structures have been elucidated by spectral data and elemental analysis. The title compounds were tested for antimicrobial activity in vitro against gram-positive bacteria (Staphylococcus aureus,and Micrococcus leuteus), gram-negative bacteria (Serratia marcescens and Escherichia coli) and some fungi (Candida albicans, Scopulariopsis brevicalus, Geotrichum candidum, Macrophomina phaseolina, Fusarium oxysporum and Trichoderma harzianum) using agar cup diffusion method. The antimicrobial activity was found to be greatly affected by the bulkiness of the side chain and the presence of polar carboxylic group. Highest activity was obtained with compounds 4a and 4k (R= CH 3 , CH 2-COOH).