New thiazol-pyridazine derivatives as antimicrobial and antiviral candidates: Synthesis, and application
In this manuscript, we are motivated to investigate the reaction site-selectivity for the hydrazo thiazole derivatives (6a–c) with different types of active methylene groups such as malononitrile, and ethyl cyanoacetate. Based on their structural investigations and spectrum data, the results of thes...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Journal of Saudi Chemical Society |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1319610324000255 |
| _version_ | 1797247924359397376 |
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| author | Fuad A. Alatawi Abdulmajeed F. Alrefaei Alaa M. Alqahtani Amerah Alsoliemy Hanadi A. Katouah Hana M. Abumelha Fawaz A. Saad Nashwa M. El-Metwaly |
| author_facet | Fuad A. Alatawi Abdulmajeed F. Alrefaei Alaa M. Alqahtani Amerah Alsoliemy Hanadi A. Katouah Hana M. Abumelha Fawaz A. Saad Nashwa M. El-Metwaly |
| author_sort | Fuad A. Alatawi |
| collection | DOAJ |
| description | In this manuscript, we are motivated to investigate the reaction site-selectivity for the hydrazo thiazole derivatives (6a–c) with different types of active methylene groups such as malononitrile, and ethyl cyanoacetate. Based on their structural investigations and spectrum data, the results of these reactions have been established to be iminopyridazines (7a–c) and 6-oxopyridazine derivatives (8a–c). We tested the ability of the newly synthesized pyridazine derivatives to inhibit the microbes and COVID-19 proteins. Human coronavirus 229E (HCoV-229E) was used to investigate the antiviral efficacy of prepared compounds. Green monkey kidney (Vero-E6) cell lines were used to investigate MTT and cytopathic effect (CPE). The new 6-oxopyridazine derivatives (8a–c) revealed significant inhibitory efficacy and were capable of inhibiting the human coronavirus 229E. Moreover, the antimicrobial result showed that compounds iminopyridazine (7c) followed by iminopyridazine (7a) followed by iminopyridazine (7b) exhibited excellent antimicrobial properties toward all utilized strains, usually greater than that of common reference drugs, with MIC values ranging from 13 to 21 ppm, from 9 to 14 ppm, and from 8 to 19 ppm whereas, the remaining substances appeared to be promising effective. Structure-activity relationship (SAR) revealed that pyridazine scaffolds containing NH group, as well as substituted electron withdrawal group (Cl) in para-position for benzene ring attributed to thiazole moiety have the best activity. The current study successfully illustrated the possible application of heterocyclic derivatives with pyridazie nucleus including thiazole ring as the main compound in the development of dual antiviral (COVID-19) and antibacterial pharmaceuticals in the future. |
| first_indexed | 2024-03-07T14:29:47Z |
| format | Article |
| id | doaj.art-212cbe2c91ee4c16a1a045febe141ffc |
| institution | Directory Open Access Journal |
| issn | 1319-6103 |
| language | English |
| last_indexed | 2024-04-24T20:06:25Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Saudi Chemical Society |
| spelling | doaj.art-212cbe2c91ee4c16a1a045febe141ffc2024-03-24T06:56:46ZengElsevierJournal of Saudi Chemical Society1319-61032024-03-01282101830New thiazol-pyridazine derivatives as antimicrobial and antiviral candidates: Synthesis, and applicationFuad A. Alatawi0Abdulmajeed F. Alrefaei1Alaa M. Alqahtani2Amerah Alsoliemy3Hanadi A. Katouah4Hana M. Abumelha5Fawaz A. Saad6Nashwa M. El-Metwaly7Department of Biology, Faculty of Science, University of Tabuk, Tabuk 71491, Saudi ArabiaDepartment of Biology/Genetic and Molecular Biology Central Laboratory (GMCL), Jamoum University College, Umm Al-Qura University, Makkah 2203, Saudi ArabiaDepartment of Pharmaceutical Sciences, Faculty of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi ArabiaDepartment of Chemistry, Faculty of Science, Umm Al-Qura University, Makkah 24230, Saudi ArabiaDepartment of Chemistry, Faculty of Science, Umm Al-Qura University, Makkah 24230, Saudi ArabiaDepartment of Chemistry, College of Science, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi ArabiaDepartment of Chemistry, Faculty of Science, Umm Al-Qura University, Makkah 24230, Saudi ArabiaDepartment of Chemistry, Faculty of Science, Umm Al-Qura University, Makkah 24230, Saudi Arabia; Department of Chemistry, Faculty of Science, Mansoura University, El-Gomhoria Street 35516, Egypt; Corresponding author at: Department of Chemistry, Faculty of Science, Umm Al-Qura University, Makkah 24230, Saudi Arabia.In this manuscript, we are motivated to investigate the reaction site-selectivity for the hydrazo thiazole derivatives (6a–c) with different types of active methylene groups such as malononitrile, and ethyl cyanoacetate. Based on their structural investigations and spectrum data, the results of these reactions have been established to be iminopyridazines (7a–c) and 6-oxopyridazine derivatives (8a–c). We tested the ability of the newly synthesized pyridazine derivatives to inhibit the microbes and COVID-19 proteins. Human coronavirus 229E (HCoV-229E) was used to investigate the antiviral efficacy of prepared compounds. Green monkey kidney (Vero-E6) cell lines were used to investigate MTT and cytopathic effect (CPE). The new 6-oxopyridazine derivatives (8a–c) revealed significant inhibitory efficacy and were capable of inhibiting the human coronavirus 229E. Moreover, the antimicrobial result showed that compounds iminopyridazine (7c) followed by iminopyridazine (7a) followed by iminopyridazine (7b) exhibited excellent antimicrobial properties toward all utilized strains, usually greater than that of common reference drugs, with MIC values ranging from 13 to 21 ppm, from 9 to 14 ppm, and from 8 to 19 ppm whereas, the remaining substances appeared to be promising effective. Structure-activity relationship (SAR) revealed that pyridazine scaffolds containing NH group, as well as substituted electron withdrawal group (Cl) in para-position for benzene ring attributed to thiazole moiety have the best activity. The current study successfully illustrated the possible application of heterocyclic derivatives with pyridazie nucleus including thiazole ring as the main compound in the development of dual antiviral (COVID-19) and antibacterial pharmaceuticals in the future.http://www.sciencedirect.com/science/article/pii/S1319610324000255Thiazol-2-aminesHydrazothiazoleIminopyridazines6-OxopyridazinesAnti-bacterial activityAnti-viral activity |
| spellingShingle | Fuad A. Alatawi Abdulmajeed F. Alrefaei Alaa M. Alqahtani Amerah Alsoliemy Hanadi A. Katouah Hana M. Abumelha Fawaz A. Saad Nashwa M. El-Metwaly New thiazol-pyridazine derivatives as antimicrobial and antiviral candidates: Synthesis, and application Journal of Saudi Chemical Society Thiazol-2-amines Hydrazothiazole Iminopyridazines 6-Oxopyridazines Anti-bacterial activity Anti-viral activity |
| title | New thiazol-pyridazine derivatives as antimicrobial and antiviral candidates: Synthesis, and application |
| title_full | New thiazol-pyridazine derivatives as antimicrobial and antiviral candidates: Synthesis, and application |
| title_fullStr | New thiazol-pyridazine derivatives as antimicrobial and antiviral candidates: Synthesis, and application |
| title_full_unstemmed | New thiazol-pyridazine derivatives as antimicrobial and antiviral candidates: Synthesis, and application |
| title_short | New thiazol-pyridazine derivatives as antimicrobial and antiviral candidates: Synthesis, and application |
| title_sort | new thiazol pyridazine derivatives as antimicrobial and antiviral candidates synthesis and application |
| topic | Thiazol-2-amines Hydrazothiazole Iminopyridazines 6-Oxopyridazines Anti-bacterial activity Anti-viral activity |
| url | http://www.sciencedirect.com/science/article/pii/S1319610324000255 |
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