Imidazothiazole Derivatives Exhibited Potent Effects against Brain-Eating Amoebae
<i>Naegleria fowleri (N. fowleri)</i> is a free-living, unicellular, opportunistic protist responsible for the fatal central nervous system infection, primary amoebic meningoencephalitis (PAM). Given the increase in temperatures due to global warming and climate change, it is estimated t...
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MDPI AG
2022-10-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/11/11/1515 |
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| author | Ruqaiyyah Siddiqui Mohammed I. El-Gamal Anania Boghossian Balsam Qubais Saeed Chang-Hyun Oh Mohammed S. Abdel-Maksoud Ahmad M. Alharbi Hasan Alfahemi Naveed Ahmed Khan |
| author_facet | Ruqaiyyah Siddiqui Mohammed I. El-Gamal Anania Boghossian Balsam Qubais Saeed Chang-Hyun Oh Mohammed S. Abdel-Maksoud Ahmad M. Alharbi Hasan Alfahemi Naveed Ahmed Khan |
| author_sort | Ruqaiyyah Siddiqui |
| collection | DOAJ |
| description | <i>Naegleria fowleri (N. fowleri)</i> is a free-living, unicellular, opportunistic protist responsible for the fatal central nervous system infection, primary amoebic meningoencephalitis (PAM). Given the increase in temperatures due to global warming and climate change, it is estimated that the cases of PAM are on the rise. However, there is a current lack of awareness and effective drugs, meaning there is an urgent need to develop new therapeutic drugs. In this study, the target compounds were synthesized and tested for their anti-amoebic properties against <i>N. fowleri.</i> Most compounds exhibited significant amoebicidal effects against <i>N. fowleri</i>; for example, <b>1h</b>, <b>1j</b>, and <b>1q</b> reduced <i>N. fowleri’s</i> viability to 15.14%, 17.45% and 28.78%, respectively. Furthermore, the majority of the compounds showed reductions in amoeba-mediated host death. Of interest are the compounds <b>1f</b>, <b>1k</b>, and <b>1v</b>, as they were capable of reducing the amoeba-mediated host cell death to 52.3%, 51%, and 56.9% from 100%, respectively. Additionally, these compounds exhibit amoebicidal properties as well; they were found to decrease <i>N. fowleri’s</i> viability to 26.41%, 27.39%, and 24.13% from 100%, respectively. Moreover, the MIC<sub>50</sub> values for <b>1e</b>, <b>1f</b>, and <b>1h</b> were determined to be 48.45 µM, 60.87 µM, and 50.96 µM, respectively. Additionally, the majority of compounds were found to exhibit limited cytotoxicity, except for <b>1l</b>, <b>1o</b>, <b>1p</b>, <b>1m</b>, <b>1c</b>, <b>1b</b>, <b>1zb</b>, <b>1z</b>, <b>1y</b>, and <b>1x</b>, which exhibited negligible toxicity. It is anticipated that these compounds may be developed further as effective treatments against these devastating infections due to brain-eating amoebae. |
| first_indexed | 2024-03-09T19:20:16Z |
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| id | doaj.art-95735210b1954db4a9dcb366100dad81 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-09T19:20:16Z |
| publishDate | 2022-10-01 |
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| spelling | doaj.art-95735210b1954db4a9dcb366100dad812023-11-24T03:27:39ZengMDPI AGAntibiotics2079-63822022-10-011111151510.3390/antibiotics11111515Imidazothiazole Derivatives Exhibited Potent Effects against Brain-Eating AmoebaeRuqaiyyah Siddiqui0Mohammed I. El-Gamal1Anania Boghossian2Balsam Qubais Saeed3Chang-Hyun Oh4Mohammed S. Abdel-Maksoud5Ahmad M. Alharbi6Hasan Alfahemi7Naveed Ahmed Khan8College of Arts and Sciences, American University of Sharjah, Sharjah 26666, United Arab EmiratesDepartment of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab EmiratesCollege of Arts and Sciences, American University of Sharjah, Sharjah 26666, United Arab EmiratesSharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab EmiratesCenter of Biomaterials, Korea Institute of Science & Technology (KIST School), Seongbuk-gu, Seoul 02792, KoreaMedicinal & Pharmaceutical Chemistry Department, Pharmaceutical and Drug Industries Research Division, National Research Centre (NRC), Dokki, Giza 12622, EgyptDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif 21944, Saudi ArabiaDepartment of Medical Microbiology, Faculty of Medicine, Al-Baha University, Al-Baha 65799, Saudi ArabiaDepartment of Medical Biology, Faculty of Medicine, Istinye University, Istanbul 34010, Turkey<i>Naegleria fowleri (N. fowleri)</i> is a free-living, unicellular, opportunistic protist responsible for the fatal central nervous system infection, primary amoebic meningoencephalitis (PAM). Given the increase in temperatures due to global warming and climate change, it is estimated that the cases of PAM are on the rise. However, there is a current lack of awareness and effective drugs, meaning there is an urgent need to develop new therapeutic drugs. In this study, the target compounds were synthesized and tested for their anti-amoebic properties against <i>N. fowleri.</i> Most compounds exhibited significant amoebicidal effects against <i>N. fowleri</i>; for example, <b>1h</b>, <b>1j</b>, and <b>1q</b> reduced <i>N. fowleri’s</i> viability to 15.14%, 17.45% and 28.78%, respectively. Furthermore, the majority of the compounds showed reductions in amoeba-mediated host death. Of interest are the compounds <b>1f</b>, <b>1k</b>, and <b>1v</b>, as they were capable of reducing the amoeba-mediated host cell death to 52.3%, 51%, and 56.9% from 100%, respectively. Additionally, these compounds exhibit amoebicidal properties as well; they were found to decrease <i>N. fowleri’s</i> viability to 26.41%, 27.39%, and 24.13% from 100%, respectively. Moreover, the MIC<sub>50</sub> values for <b>1e</b>, <b>1f</b>, and <b>1h</b> were determined to be 48.45 µM, 60.87 µM, and 50.96 µM, respectively. Additionally, the majority of compounds were found to exhibit limited cytotoxicity, except for <b>1l</b>, <b>1o</b>, <b>1p</b>, <b>1m</b>, <b>1c</b>, <b>1b</b>, <b>1zb</b>, <b>1z</b>, <b>1y</b>, and <b>1x</b>, which exhibited negligible toxicity. It is anticipated that these compounds may be developed further as effective treatments against these devastating infections due to brain-eating amoebae.https://www.mdpi.com/2079-6382/11/11/1515<i>Naegleria fowleri</i>amoebicidalanti-amoebicmortalitycytotoxicitycytopathogenicity |
| spellingShingle | Ruqaiyyah Siddiqui Mohammed I. El-Gamal Anania Boghossian Balsam Qubais Saeed Chang-Hyun Oh Mohammed S. Abdel-Maksoud Ahmad M. Alharbi Hasan Alfahemi Naveed Ahmed Khan Imidazothiazole Derivatives Exhibited Potent Effects against Brain-Eating Amoebae Antibiotics <i>Naegleria fowleri</i> amoebicidal anti-amoebic mortality cytotoxicity cytopathogenicity |
| title | Imidazothiazole Derivatives Exhibited Potent Effects against Brain-Eating Amoebae |
| title_full | Imidazothiazole Derivatives Exhibited Potent Effects against Brain-Eating Amoebae |
| title_fullStr | Imidazothiazole Derivatives Exhibited Potent Effects against Brain-Eating Amoebae |
| title_full_unstemmed | Imidazothiazole Derivatives Exhibited Potent Effects against Brain-Eating Amoebae |
| title_short | Imidazothiazole Derivatives Exhibited Potent Effects against Brain-Eating Amoebae |
| title_sort | imidazothiazole derivatives exhibited potent effects against brain eating amoebae |
| topic | <i>Naegleria fowleri</i> amoebicidal anti-amoebic mortality cytotoxicity cytopathogenicity |
| url | https://www.mdpi.com/2079-6382/11/11/1515 |
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