Synthetic (<i>E</i>)-3-Phenyl-5-(phenylamino)-2-styryl-1,3,4-thiadiazol-3-ium Chloride Derivatives as Promising Chemotherapy Agents on Cell Lines Infected with HTLV-1
Synthesis of four compounds belonging to mesoionic class, (<i>E</i>)-3-phenyl-5-(phenylamino)-2-styryl-1,3,4-thiadiazol-3-ium chloride derivatives (<b>5a</b>–<b>d</b>) and their biological evaluation against MT2 and C92 cell lines infected with human T-cell lympho...
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| Format: | Article |
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MDPI AG
2020-05-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/11/2537 |
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| author | Danilo Sousa-Pereira Thais Silva de Oliveira Rojane O. Paiva Otávio Augusto Chaves José C. Netto-Ferreira Juliana Echevarria-Lima Aurea Echevarria |
| author_facet | Danilo Sousa-Pereira Thais Silva de Oliveira Rojane O. Paiva Otávio Augusto Chaves José C. Netto-Ferreira Juliana Echevarria-Lima Aurea Echevarria |
| author_sort | Danilo Sousa-Pereira |
| collection | DOAJ |
| description | Synthesis of four compounds belonging to mesoionic class, (<i>E</i>)-3-phenyl-5-(phenylamino)-2-styryl-1,3,4-thiadiazol-3-ium chloride derivatives (<b>5a</b>–<b>d</b>) and their biological evaluation against MT2 and C92 cell lines infected with human T-cell lymphotropic virus type-1 (HTLV-1), which causes adult T-cell leukemia/lymphoma (ATLL), and non-infected cell lines (Jurkat) are reported. The compounds were obtained by convergent synthesis under microwave irradiation and the cytotoxicity was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Results showed IC<sub>50</sub> values of all compounds in the range of 1.51–7.70 μM in HTLV-1-infected and non-infected cells. Furthermore, it was observed that <b>5b</b> could induce necrosis after 24 h for Jurkat and MT2 cell lines. The experimental (fluorimetric method) and theoretical (molecular docking) results suggested that the mechanism of action for <b>5b</b> could be related to its capacity to intercalate into DNA. Moreover, the preliminary pharmacokinetic profile of the studied compounds (<b>5a</b>–<b>d</b>) was obtained through human serum albumin (HSA) binding affinity using multiple spectroscopic techniques (circular dichroism, steady-state and time-resolved fluorescence), zeta potential and molecular docking calculations. The interaction HSA:<b>5a</b>–<b>d</b> is spontaneous and moderate (<i>K<sub>a</sub></i> ~ 10<sup>4</sup> M<sup>−1</sup>) via a ground-state association, without significantly perturbing both the secondary and surface structures of the albumin in the subdomain IIA (site I), indicating feasible biodistribution in the human bloodstream. |
| first_indexed | 2024-03-10T19:29:47Z |
| format | Article |
| id | doaj.art-8c583559d716454785ffa71953985549 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T19:29:47Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-8c583559d716454785ffa719539855492023-11-20T02:12:51ZengMDPI AGMolecules1420-30492020-05-012511253710.3390/molecules25112537Synthetic (<i>E</i>)-3-Phenyl-5-(phenylamino)-2-styryl-1,3,4-thiadiazol-3-ium Chloride Derivatives as Promising Chemotherapy Agents on Cell Lines Infected with HTLV-1Danilo Sousa-Pereira0Thais Silva de Oliveira1Rojane O. Paiva2Otávio Augusto Chaves3José C. Netto-Ferreira4Juliana Echevarria-Lima5Aurea Echevarria6Instituto de Química, Universidade Federal Rural do Rio de Janeiro (UFRRJ), Seropédica, Rio de Janeiro 23.890-000, BrazilLaboratório de Imunologia Básica e Aplicada, Departamento de Imunologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21.941-590, BrazilLaboratório de Imunologia Básica e Aplicada, Departamento de Imunologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21.941-590, BrazilInstituto de Química, Universidade Federal Rural do Rio de Janeiro (UFRRJ), Seropédica, Rio de Janeiro 23.890-000, BrazilInstituto de Química, Universidade Federal Rural do Rio de Janeiro (UFRRJ), Seropédica, Rio de Janeiro 23.890-000, BrazilLaboratório de Imunologia Básica e Aplicada, Departamento de Imunologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21.941-590, BrazilInstituto de Química, Universidade Federal Rural do Rio de Janeiro (UFRRJ), Seropédica, Rio de Janeiro 23.890-000, BrazilSynthesis of four compounds belonging to mesoionic class, (<i>E</i>)-3-phenyl-5-(phenylamino)-2-styryl-1,3,4-thiadiazol-3-ium chloride derivatives (<b>5a</b>–<b>d</b>) and their biological evaluation against MT2 and C92 cell lines infected with human T-cell lymphotropic virus type-1 (HTLV-1), which causes adult T-cell leukemia/lymphoma (ATLL), and non-infected cell lines (Jurkat) are reported. The compounds were obtained by convergent synthesis under microwave irradiation and the cytotoxicity was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Results showed IC<sub>50</sub> values of all compounds in the range of 1.51–7.70 μM in HTLV-1-infected and non-infected cells. Furthermore, it was observed that <b>5b</b> could induce necrosis after 24 h for Jurkat and MT2 cell lines. The experimental (fluorimetric method) and theoretical (molecular docking) results suggested that the mechanism of action for <b>5b</b> could be related to its capacity to intercalate into DNA. Moreover, the preliminary pharmacokinetic profile of the studied compounds (<b>5a</b>–<b>d</b>) was obtained through human serum albumin (HSA) binding affinity using multiple spectroscopic techniques (circular dichroism, steady-state and time-resolved fluorescence), zeta potential and molecular docking calculations. The interaction HSA:<b>5a</b>–<b>d</b> is spontaneous and moderate (<i>K<sub>a</sub></i> ~ 10<sup>4</sup> M<sup>−1</sup>) via a ground-state association, without significantly perturbing both the secondary and surface structures of the albumin in the subdomain IIA (site I), indicating feasible biodistribution in the human bloodstream.https://www.mdpi.com/1420-3049/25/11/2537mesoionic compoundsHTLV-1HSA interactionmultiple spectroscopicmolecular docking |
| spellingShingle | Danilo Sousa-Pereira Thais Silva de Oliveira Rojane O. Paiva Otávio Augusto Chaves José C. Netto-Ferreira Juliana Echevarria-Lima Aurea Echevarria Synthetic (<i>E</i>)-3-Phenyl-5-(phenylamino)-2-styryl-1,3,4-thiadiazol-3-ium Chloride Derivatives as Promising Chemotherapy Agents on Cell Lines Infected with HTLV-1 Molecules mesoionic compounds HTLV-1 HSA interaction multiple spectroscopic molecular docking |
| title | Synthetic (<i>E</i>)-3-Phenyl-5-(phenylamino)-2-styryl-1,3,4-thiadiazol-3-ium Chloride Derivatives as Promising Chemotherapy Agents on Cell Lines Infected with HTLV-1 |
| title_full | Synthetic (<i>E</i>)-3-Phenyl-5-(phenylamino)-2-styryl-1,3,4-thiadiazol-3-ium Chloride Derivatives as Promising Chemotherapy Agents on Cell Lines Infected with HTLV-1 |
| title_fullStr | Synthetic (<i>E</i>)-3-Phenyl-5-(phenylamino)-2-styryl-1,3,4-thiadiazol-3-ium Chloride Derivatives as Promising Chemotherapy Agents on Cell Lines Infected with HTLV-1 |
| title_full_unstemmed | Synthetic (<i>E</i>)-3-Phenyl-5-(phenylamino)-2-styryl-1,3,4-thiadiazol-3-ium Chloride Derivatives as Promising Chemotherapy Agents on Cell Lines Infected with HTLV-1 |
| title_short | Synthetic (<i>E</i>)-3-Phenyl-5-(phenylamino)-2-styryl-1,3,4-thiadiazol-3-ium Chloride Derivatives as Promising Chemotherapy Agents on Cell Lines Infected with HTLV-1 |
| title_sort | synthetic i e i 3 phenyl 5 phenylamino 2 styryl 1 3 4 thiadiazol 3 ium chloride derivatives as promising chemotherapy agents on cell lines infected with htlv 1 |
| topic | mesoionic compounds HTLV-1 HSA interaction multiple spectroscopic molecular docking |
| url | https://www.mdpi.com/1420-3049/25/11/2537 |
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