Exploring the Antiparasitic Activity of <i>Tris</i>-1,3,4-Thiadiazoles against <i>Toxoplasma gondii</i>-Infected Mice
Nitrogen-containing atoms in their core structures have been exclusive building blocks in drug discovery and development. One of the most significant and well-known heterocycles is the 1,3,4-thidiazole nucleus, which is found in a wide range of natural products and therapeutic agents. In the present...
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MDPI AG
2022-03-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/7/2246 |
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| author | Tahani M. Almutairi Nadjet Rezki Mohamed Reda Aouad Mohamed Hagar Basant A. Bakr Moaaz T. Hamed Maha Khairy Hassen Bassma H. Elwakil Esraa Abdelhamid Moneer |
| author_facet | Tahani M. Almutairi Nadjet Rezki Mohamed Reda Aouad Mohamed Hagar Basant A. Bakr Moaaz T. Hamed Maha Khairy Hassen Bassma H. Elwakil Esraa Abdelhamid Moneer |
| author_sort | Tahani M. Almutairi |
| collection | DOAJ |
| description | Nitrogen-containing atoms in their core structures have been exclusive building blocks in drug discovery and development. One of the most significant and well-known heterocycles is the 1,3,4-thidiazole nucleus, which is found in a wide range of natural products and therapeutic agents. In the present work, certain <i>tris</i>-1,3,4-thiadiazole derivatives (<b>6</b>, <b>7</b>) were synthesized through a multi-step synthesis approach. All synthesized compounds were characterized using different spectroscopic tools. Previously, thiadiazole compounds as anti-<i>Toxoplasma gondii</i> agents have been conducted and reported in vitro. However, this is the first study to test the anti-<i>Toxoplasma gondii</i> activity of manufactured molecular hybrids thiadiazole in an infected mouse model with the acute RH strain of <i>T. gondii</i>. All the observed results demonstrated compound (<b>7</b>)’s powerful activity, with a considerable reduction in the parasite count reaching 82.6% in brain tissues, followed by liver and spleen tissues (65.35 and 64.81%, respectively). Inflammatory and anti-inflammatory cytokines assessments proved that Compound 7 possesses potent antiparasitic effect. Furthermore, docking tests against <i>Tg</i>CDPK1 and ROP18 kinase (two major enzymes involved in parasite invasion and egression) demonstrated compound <b>7</b>’s higher potency compared to compound <b>6</b> and megazol. According to the mentioned results, <i>tris</i>-1,3,4-thiadiazole derivatives under test can be employed as potent antiparasitic agents against the acute RH strain of <i>T. gondii</i>. |
| first_indexed | 2024-03-09T11:35:59Z |
| format | Article |
| id | doaj.art-7a91f0de88414ae0949302cc0a867e89 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T11:35:59Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-7a91f0de88414ae0949302cc0a867e892023-11-30T23:41:35ZengMDPI AGMolecules1420-30492022-03-01277224610.3390/molecules27072246Exploring the Antiparasitic Activity of <i>Tris</i>-1,3,4-Thiadiazoles against <i>Toxoplasma gondii</i>-Infected MiceTahani M. Almutairi0Nadjet Rezki1Mohamed Reda Aouad2Mohamed Hagar3Basant A. Bakr4Moaaz T. Hamed5Maha Khairy Hassen6Bassma H. Elwakil7Esraa Abdelhamid Moneer8Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi ArabiaDepartment of Chemistry, Faculty of Science, Taibah University, Al-Madinah Al-Munawarah 30002, Saudi ArabiaDepartment of Chemistry, Faculty of Science, Taibah University, Al-Madinah Al-Munawarah 30002, Saudi ArabiaDepartment of Chemistry, Faculty of Science, Alexandria University, Alexandria 21321, EgyptDepartment of Zoology, Faculty of Science, Alexandria University, Alexandria 21321, EgyptDepartment of Botany and Microbiology, Faculty of Science, Alexandria University, Alexandria 21321, EgyptDepartment of Medical Laboratory Technology, Faculty of Applied Health Sciences Technology, Pharos University in Alexandria, Alexandria 21321, EgyptDepartment of Medical Laboratory Technology, Faculty of Applied Health Sciences Technology, Pharos University in Alexandria, Alexandria 21321, EgyptDepartment of Medical Laboratory Technology, Faculty of Applied Health Sciences Technology, Pharos University in Alexandria, Alexandria 21321, EgyptNitrogen-containing atoms in their core structures have been exclusive building blocks in drug discovery and development. One of the most significant and well-known heterocycles is the 1,3,4-thidiazole nucleus, which is found in a wide range of natural products and therapeutic agents. In the present work, certain <i>tris</i>-1,3,4-thiadiazole derivatives (<b>6</b>, <b>7</b>) were synthesized through a multi-step synthesis approach. All synthesized compounds were characterized using different spectroscopic tools. Previously, thiadiazole compounds as anti-<i>Toxoplasma gondii</i> agents have been conducted and reported in vitro. However, this is the first study to test the anti-<i>Toxoplasma gondii</i> activity of manufactured molecular hybrids thiadiazole in an infected mouse model with the acute RH strain of <i>T. gondii</i>. All the observed results demonstrated compound (<b>7</b>)’s powerful activity, with a considerable reduction in the parasite count reaching 82.6% in brain tissues, followed by liver and spleen tissues (65.35 and 64.81%, respectively). Inflammatory and anti-inflammatory cytokines assessments proved that Compound 7 possesses potent antiparasitic effect. Furthermore, docking tests against <i>Tg</i>CDPK1 and ROP18 kinase (two major enzymes involved in parasite invasion and egression) demonstrated compound <b>7</b>’s higher potency compared to compound <b>6</b> and megazol. According to the mentioned results, <i>tris</i>-1,3,4-thiadiazole derivatives under test can be employed as potent antiparasitic agents against the acute RH strain of <i>T. gondii</i>.https://www.mdpi.com/1420-3049/27/7/2246<i>tris-</i>1,3,4-thiadiazolesantiparasite<i>Toxoplasma gondii</i>in vivo studyimmunological studiesdocking studies |
| spellingShingle | Tahani M. Almutairi Nadjet Rezki Mohamed Reda Aouad Mohamed Hagar Basant A. Bakr Moaaz T. Hamed Maha Khairy Hassen Bassma H. Elwakil Esraa Abdelhamid Moneer Exploring the Antiparasitic Activity of <i>Tris</i>-1,3,4-Thiadiazoles against <i>Toxoplasma gondii</i>-Infected Mice Molecules <i>tris-</i>1,3,4-thiadiazoles antiparasite <i>Toxoplasma gondii</i> in vivo study immunological studies docking studies |
| title | Exploring the Antiparasitic Activity of <i>Tris</i>-1,3,4-Thiadiazoles against <i>Toxoplasma gondii</i>-Infected Mice |
| title_full | Exploring the Antiparasitic Activity of <i>Tris</i>-1,3,4-Thiadiazoles against <i>Toxoplasma gondii</i>-Infected Mice |
| title_fullStr | Exploring the Antiparasitic Activity of <i>Tris</i>-1,3,4-Thiadiazoles against <i>Toxoplasma gondii</i>-Infected Mice |
| title_full_unstemmed | Exploring the Antiparasitic Activity of <i>Tris</i>-1,3,4-Thiadiazoles against <i>Toxoplasma gondii</i>-Infected Mice |
| title_short | Exploring the Antiparasitic Activity of <i>Tris</i>-1,3,4-Thiadiazoles against <i>Toxoplasma gondii</i>-Infected Mice |
| title_sort | exploring the antiparasitic activity of i tris i 1 3 4 thiadiazoles against i toxoplasma gondii i infected mice |
| topic | <i>tris-</i>1,3,4-thiadiazoles antiparasite <i>Toxoplasma gondii</i> in vivo study immunological studies docking studies |
| url | https://www.mdpi.com/1420-3049/27/7/2246 |
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