Synthesis and molecular modeling of new triazole-bithiazole conjugates as antimicrobial agents
A series of new triazole-bithiazole conjugates were synthesized through a sequence of reactions started by chloroacetylation of 2-amino-4-triazolyl-thiazole compound 2. The various spectroscopic techniques, such as IR, NMR and MS, confirmed the suggested chemical structure of isolated hybrids. The D...
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Elsevier
2024-12-01
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| Series: | Results in Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211715624006210 |
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| author | Hadeer Mattar Gadeer R.S. Ashour Mansoor Alsahag Ali Alisaac Matokah M. Abualnaja Adel I. Alalawy Fatmah O. Sefrji Nashwa M. El-Metwaly |
| author_facet | Hadeer Mattar Gadeer R.S. Ashour Mansoor Alsahag Ali Alisaac Matokah M. Abualnaja Adel I. Alalawy Fatmah O. Sefrji Nashwa M. El-Metwaly |
| author_sort | Hadeer Mattar |
| collection | DOAJ |
| description | A series of new triazole-bithiazole conjugates were synthesized through a sequence of reactions started by chloroacetylation of 2-amino-4-triazolyl-thiazole compound 2. The various spectroscopic techniques, such as IR, NMR and MS, confirmed the suggested chemical structure of isolated hybrids. The DFT studies of the produced derivatives revealed twisted configuration except for the parent 2, how was planar. In addition, the researched conjugates presented extended FMO’s energy gap (ΔEH-L) from 2.60 to 4.64 eV and could be sorted as 5b < 9b < 5a < 9a < 4 < 8 < 2 < 7 < 3. The antibacterial and antifungal activity of the newly synthesized conjugates has been examined using the minimum inhibitory concentration (MIC) method against representative pathogens. The data revealed that conjugates 9a and 9b exhibited significant activity, compared to standard antimicrobial agents, ampicillin, and fluconazole. Moreover, the DNA gyrase enzyme inhibitory action of the synthesized triazole-bithiazoles was assessed and compared to novobiocin (Novo) as a standard inhibitor. Furthermore, the interaction of the synthesized conjugates with the amino acid residues of a target protein has been empathized via docking study, which cleared that conjugate 9b has the greatest binding affinity among the produced conjugates, showing its potential as an antibacterial agent. Finally, the pharmacokinetic properties of synthesized hybrids were ascribed using the SwissADME indicating good bioavailability for conjugates 3, 4, and 7, while others, including 5a, 5b, 8, 9a, and 9b, faced challenges related to low GI absorption and Lipinski violations. |
| format | Article |
| id | doaj-art-88e7eb6d047e42cc91240cbb44a98f99 |
| institution | DOAJ |
| issn | 2211-7156 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Results in Chemistry |
| spelling | doaj-art-88e7eb6d047e42cc91240cbb44a98f992025-08-20T02:49:59ZengElsevierResults in Chemistry2211-71562024-12-011210192510.1016/j.rechem.2024.101925Synthesis and molecular modeling of new triazole-bithiazole conjugates as antimicrobial agentsHadeer Mattar0Gadeer R.S. Ashour1Mansoor Alsahag2Ali Alisaac3Matokah M. Abualnaja4Adel I. Alalawy5Fatmah O. Sefrji6Nashwa M. El-Metwaly7Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Al-Baha University, Saudi ArabiaDepartment of Chemistry, Faculty of Science, Umm Al-Qura University, Makkah 24230, Saudi ArabiaDepartment of Laboratory Medicine, Faculty of Applied Medical Sciences, Al-Baha University, Saudi ArabiaDepartment of Laboratory Medicine, Faculty of Applied Medical Sciences, Al-Baha University, Saudi ArabiaDepartment of Chemistry, Faculty of Science, Umm Al-Qura University, Makkah 24230, Saudi ArabiaDepartment of Biochemistry, Faculty of Science, University of Tabuk, Saudi ArabiaDepartment of Biology, College of Science, Taibah University, Al-Madinah Al-Munawarah, 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.A series of new triazole-bithiazole conjugates were synthesized through a sequence of reactions started by chloroacetylation of 2-amino-4-triazolyl-thiazole compound 2. The various spectroscopic techniques, such as IR, NMR and MS, confirmed the suggested chemical structure of isolated hybrids. The DFT studies of the produced derivatives revealed twisted configuration except for the parent 2, how was planar. In addition, the researched conjugates presented extended FMO’s energy gap (ΔEH-L) from 2.60 to 4.64 eV and could be sorted as 5b < 9b < 5a < 9a < 4 < 8 < 2 < 7 < 3. The antibacterial and antifungal activity of the newly synthesized conjugates has been examined using the minimum inhibitory concentration (MIC) method against representative pathogens. The data revealed that conjugates 9a and 9b exhibited significant activity, compared to standard antimicrobial agents, ampicillin, and fluconazole. Moreover, the DNA gyrase enzyme inhibitory action of the synthesized triazole-bithiazoles was assessed and compared to novobiocin (Novo) as a standard inhibitor. Furthermore, the interaction of the synthesized conjugates with the amino acid residues of a target protein has been empathized via docking study, which cleared that conjugate 9b has the greatest binding affinity among the produced conjugates, showing its potential as an antibacterial agent. Finally, the pharmacokinetic properties of synthesized hybrids were ascribed using the SwissADME indicating good bioavailability for conjugates 3, 4, and 7, while others, including 5a, 5b, 8, 9a, and 9b, faced challenges related to low GI absorption and Lipinski violations.http://www.sciencedirect.com/science/article/pii/S2211715624006210Triazolyl-thiazoleThioureaAmmonium thiocyanateDFT calculationsFMO’sAntimicrobial |
| spellingShingle | Hadeer Mattar Gadeer R.S. Ashour Mansoor Alsahag Ali Alisaac Matokah M. Abualnaja Adel I. Alalawy Fatmah O. Sefrji Nashwa M. El-Metwaly Synthesis and molecular modeling of new triazole-bithiazole conjugates as antimicrobial agents Results in Chemistry Triazolyl-thiazole Thiourea Ammonium thiocyanate DFT calculations FMO’s Antimicrobial |
| title | Synthesis and molecular modeling of new triazole-bithiazole conjugates as antimicrobial agents |
| title_full | Synthesis and molecular modeling of new triazole-bithiazole conjugates as antimicrobial agents |
| title_fullStr | Synthesis and molecular modeling of new triazole-bithiazole conjugates as antimicrobial agents |
| title_full_unstemmed | Synthesis and molecular modeling of new triazole-bithiazole conjugates as antimicrobial agents |
| title_short | Synthesis and molecular modeling of new triazole-bithiazole conjugates as antimicrobial agents |
| title_sort | synthesis and molecular modeling of new triazole bithiazole conjugates as antimicrobial agents |
| topic | Triazolyl-thiazole Thiourea Ammonium thiocyanate DFT calculations FMO’s Antimicrobial |
| url | http://www.sciencedirect.com/science/article/pii/S2211715624006210 |
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