In Vitro and in Vivo Assays of 3,5-Disubstituted-Tetrahydro-2H-1,3,5-Thiadiazin-2-Thione Derivatives against Trypanosoma cruzi
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...
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| Format: | Article |
| Language: | English |
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Fundação Oswaldo Cruz (FIOCRUZ)
2002-03-01
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| Series: | Memorias do Instituto Oswaldo Cruz |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762002000200023 |
| _version_ | 1797715748544577536 |
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| author | Susana Muelas Margarita Suárez Rolando Pérez Hortensia Rodríguez Carmen Ochoa José Antonio Escario Alicia Gómez-Barrio |
| author_facet | Susana Muelas Margarita Suárez Rolando Pérez Hortensia Rodríguez Carmen Ochoa José Antonio Escario Alicia Gómez-Barrio |
| author_sort | Susana Muelas |
| collection | DOAJ |
| description | 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. Anti-amastigote 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. |
| first_indexed | 2024-03-12T08:11:20Z |
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| id | doaj.art-f2499a187a30463e940085fb729c6de0 |
| institution | Directory Open Access Journal |
| issn | 0074-0276 1678-8060 |
| language | English |
| last_indexed | 2024-03-12T08:11:20Z |
| publishDate | 2002-03-01 |
| publisher | Fundação Oswaldo Cruz (FIOCRUZ) |
| record_format | Article |
| series | Memorias do Instituto Oswaldo Cruz |
| spelling | doaj.art-f2499a187a30463e940085fb729c6de02023-09-02T19:07:06ZengFundação Oswaldo Cruz (FIOCRUZ)Memorias do Instituto Oswaldo Cruz0074-02761678-80602002-03-0197226927210.1590/S0074-02762002000200023In Vitro and in Vivo Assays of 3,5-Disubstituted-Tetrahydro-2H-1,3,5-Thiadiazin-2-Thione Derivatives against Trypanosoma cruziSusana MuelasMargarita SuárezRolando PérezHortensia RodríguezCarmen OchoaJosé Antonio EscarioAlicia Gómez-BarrioCytotoxicity 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. Anti-amastigote 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.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762002000200023antichagasic drugsamastigotesJ774 macrophagescytotoxicity assaysantitrypanosomal activity assaysthiadiazine thione derivatives |
| spellingShingle | Susana Muelas Margarita Suárez Rolando Pérez Hortensia Rodríguez Carmen Ochoa José Antonio Escario Alicia Gómez-Barrio In Vitro and in Vivo Assays of 3,5-Disubstituted-Tetrahydro-2H-1,3,5-Thiadiazin-2-Thione Derivatives against Trypanosoma cruzi Memorias do Instituto Oswaldo Cruz antichagasic drugs amastigotes J774 macrophages cytotoxicity assays antitrypanosomal activity assays thiadiazine thione derivatives |
| title | In Vitro and in Vivo Assays of 3,5-Disubstituted-Tetrahydro-2H-1,3,5-Thiadiazin-2-Thione Derivatives against Trypanosoma cruzi |
| title_full | In Vitro and in Vivo Assays of 3,5-Disubstituted-Tetrahydro-2H-1,3,5-Thiadiazin-2-Thione Derivatives against Trypanosoma cruzi |
| title_fullStr | In Vitro and in Vivo Assays of 3,5-Disubstituted-Tetrahydro-2H-1,3,5-Thiadiazin-2-Thione Derivatives against Trypanosoma cruzi |
| title_full_unstemmed | In Vitro and in Vivo Assays of 3,5-Disubstituted-Tetrahydro-2H-1,3,5-Thiadiazin-2-Thione Derivatives against Trypanosoma cruzi |
| title_short | In Vitro and in Vivo Assays of 3,5-Disubstituted-Tetrahydro-2H-1,3,5-Thiadiazin-2-Thione Derivatives against Trypanosoma cruzi |
| title_sort | in vitro and in vivo assays of 3 5 disubstituted tetrahydro 2h 1 3 5 thiadiazin 2 thione derivatives against trypanosoma cruzi |
| topic | antichagasic drugs amastigotes J774 macrophages cytotoxicity assays antitrypanosomal activity assays thiadiazine thione derivatives |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762002000200023 |
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