Design, synthesis, biological evaluation and in silico studies of novel 1,2,3-triazole linked benzoxazine-2,4-dione conjugates as potent antimicrobial, antioxidant and anti-inflammatory agents
In an attempt to rationalize the search for new potential anti-inflammatory and anti-infection agents, a new series of 1,4-and 1,5-disubstituted 1,2,3-triazoles linked benzoxazine conjugates have been synthesized via “Click Chemistry” reaction, were designed, synthesized and characterized by means o...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-11-01
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| Series: | Arabian Journal of Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1878535222005421 |
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| author | Manel Ben Hammouda Iqrar Ahmad Assia Hamdi Amal Dbeibia Harun Patel Nouha Bouali Walid Sabri Hamadou Karim Hosni Siwar Ghannay Fahad Alminderej Emira Noumi Mejdi Snoussi Kaïss Aouadi Adel Kadri |
| author_facet | Manel Ben Hammouda Iqrar Ahmad Assia Hamdi Amal Dbeibia Harun Patel Nouha Bouali Walid Sabri Hamadou Karim Hosni Siwar Ghannay Fahad Alminderej Emira Noumi Mejdi Snoussi Kaïss Aouadi Adel Kadri |
| author_sort | Manel Ben Hammouda |
| collection | DOAJ |
| description | In an attempt to rationalize the search for new potential anti-inflammatory and anti-infection agents, a new series of 1,4-and 1,5-disubstituted 1,2,3-triazoles linked benzoxazine conjugates have been synthesized via “Click Chemistry” reaction, were designed, synthesized and characterized by means of spectral and elemental data. The newly synthesized compounds have been assessed for their antimicrobial, antioxidant and anti-inflammatory potential. Results revealed that all synthesized compounds display superior activities to the standard drug against different bacterial strains especially S. aureus, M. luteus, and P. aeruginosa, with good to moderate activity towards the tested E. coli bacteria, in respect to the commercial antibiotic, tetracycline. Moreover, the antifungal activity was screened against C. albicans and C. krusei yeasts and results demonstrate potent activity as compared to the standard drug, ampicillin. The antioxidant activity was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging assays, whose results indicate that analogues 4a (IC50 1.88 ± 0.07 µM and 2.17 ± 0.02) followed by 4b (IC50 2.19 ± 0.09 µM and 2.38 ± 0.43 µM), 4d (IC50 2.30 ± 0.01 µM and 4.07 ± 0.57 µM), and 4f (2.98 ± 0.02 µM and 3.80 ± 0.01 µM), respectively, exhibited the strongest activity when compared to the standard reference, butylated hydroxytoluene (BHT) (3.52 ± 0.08 µM and 4.64 ± 0.11 µM). In addition, their anti-inflammatory activity was assessed using the xylene-induced ear edema standard technique and the results demonstrated the potency of 4a, 4b and 4d as excellent anti-inflammatory agents. Preliminary structure–activity relationship studies (SARs) provide those biological activities can be modulated by the presence of unsubstituted aromatic ring as well as the position of substituents on the phenyl moiety via electron withdrawing groups (EWGs) or electron donating groups (EDGs) effects. Docking studies on the most promising compounds 4a, 4b, and 4d into the active sites of S. aureus tyrosyl-tRNA synthetase, Candida albicans N-Myristoyltransferase, Human COX-2 enzyme, and Human Peroxiredoxin 5 revealed good binding profiles with the target proteins. The interaction's stability was further assessed using a conventional atomistic 100 ns dynamic simulation study. Hence, our results recommended the rationalized targets 4a, 4b and 4d, to be promising lead candidates for the discovery of novel dual anti-inflammatory and anti-infection agents. |
| first_indexed | 2024-04-11T19:15:05Z |
| format | Article |
| id | doaj.art-15813706e950483d8953de28e58c2d66 |
| institution | Directory Open Access Journal |
| issn | 1878-5352 |
| language | English |
| last_indexed | 2024-04-11T19:15:05Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Arabian Journal of Chemistry |
| spelling | doaj.art-15813706e950483d8953de28e58c2d662022-12-22T04:07:27ZengElsevierArabian Journal of Chemistry1878-53522022-11-011511104226Design, synthesis, biological evaluation and in silico studies of novel 1,2,3-triazole linked benzoxazine-2,4-dione conjugates as potent antimicrobial, antioxidant and anti-inflammatory agentsManel Ben Hammouda0Iqrar Ahmad1Assia Hamdi2Amal Dbeibia3Harun Patel4Nouha Bouali5Walid Sabri Hamadou6Karim Hosni7Siwar Ghannay8Fahad Alminderej9Emira Noumi10Mejdi Snoussi11Kaïss Aouadi12Adel Kadri13Laboratory of Heterocyclic Chemistry Natural Product and Reactivity/CHPNR, Department of Chemistry, Faculty of Science of Monastir, 5000 Monastir, TunisiaDivision of Computer Aided Drug Design, Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra 425 405, India; Corresponding authors at: Department of Chemistry, Faculty of Science and Arts of Baljurashi, Albaha University, Saudi Arabia.Laboratory of Analysis, Treatment and Valorization of Environmental Polluants and Products, Faculty of Pharmacy, Monastir University, TunisiaLaboratoire de développement chimique, galénique et pharmacologique des médicaments/Laboratory of Chemical, Pharmaceutical and Pharmacological Development of Drugs), Faculty of Pharmacy, Monastir, TunisiaDivision of Computer Aided Drug Design, Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra 425 405, IndiaDepartment of Biology, University of Ha'il, College of Science, P.O. Box 2440, Ha’il 2440, Saudi ArabiaDepartment of Biology, University of Ha'il, College of Science, P.O. Box 2440, Ha’il 2440, Saudi ArabiaLaboratoire des Substances Naturelles, Institut National de Recherche et d’Analyse Physico-chimique, Biotechp̂ole Sidi Thabet, 2020, TunisiaDepartment of Chemistry, College of Science, Qassim University, Buraidah 51452, Saudi ArabiaDepartment of Chemistry, College of Science, Qassim University, Buraidah 51452, Saudi ArabiaDepartment of Biology, University of Ha'il, College of Science, P.O. Box 2440, Ha’il 2440, Saudi Arabia; Laboratory of Genetics, Biodiversity and Valorisation of Bioressources, High Institute of Biotechnology-University of Monastir, Monastir 5000, TunisiaDepartment of Biology, University of Ha'il, College of Science, P.O. Box 2440, Ha’il 2440, Saudi Arabia; Laboratory of Genetics, Biodiversity and Valorisation of Bioressources, High Institute of Biotechnology-University of Monastir, Monastir 5000, TunisiaDepartment of Chemistry, College of Science, Qassim University, Buraidah 51452, Saudi Arabia; University of Monastir, Faculty of Science of Monastir, Avenue of the Environment, 5019 Monastir, TunisiaDepartment of Chemistry, Faculty of Science and Arts of Baljurashi, Albaha University, Saudi Arabia; Faculty of Science of Sfax, Department of Chemistry, University of Sfax, B.P. 1171, 3000 Sfax, Tunisia; Corresponding authors at: Department of Chemistry, Faculty of Science and Arts of Baljurashi, Albaha University, Saudi Arabia.In an attempt to rationalize the search for new potential anti-inflammatory and anti-infection agents, a new series of 1,4-and 1,5-disubstituted 1,2,3-triazoles linked benzoxazine conjugates have been synthesized via “Click Chemistry” reaction, were designed, synthesized and characterized by means of spectral and elemental data. The newly synthesized compounds have been assessed for their antimicrobial, antioxidant and anti-inflammatory potential. Results revealed that all synthesized compounds display superior activities to the standard drug against different bacterial strains especially S. aureus, M. luteus, and P. aeruginosa, with good to moderate activity towards the tested E. coli bacteria, in respect to the commercial antibiotic, tetracycline. Moreover, the antifungal activity was screened against C. albicans and C. krusei yeasts and results demonstrate potent activity as compared to the standard drug, ampicillin. The antioxidant activity was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging assays, whose results indicate that analogues 4a (IC50 1.88 ± 0.07 µM and 2.17 ± 0.02) followed by 4b (IC50 2.19 ± 0.09 µM and 2.38 ± 0.43 µM), 4d (IC50 2.30 ± 0.01 µM and 4.07 ± 0.57 µM), and 4f (2.98 ± 0.02 µM and 3.80 ± 0.01 µM), respectively, exhibited the strongest activity when compared to the standard reference, butylated hydroxytoluene (BHT) (3.52 ± 0.08 µM and 4.64 ± 0.11 µM). In addition, their anti-inflammatory activity was assessed using the xylene-induced ear edema standard technique and the results demonstrated the potency of 4a, 4b and 4d as excellent anti-inflammatory agents. Preliminary structure–activity relationship studies (SARs) provide those biological activities can be modulated by the presence of unsubstituted aromatic ring as well as the position of substituents on the phenyl moiety via electron withdrawing groups (EWGs) or electron donating groups (EDGs) effects. Docking studies on the most promising compounds 4a, 4b, and 4d into the active sites of S. aureus tyrosyl-tRNA synthetase, Candida albicans N-Myristoyltransferase, Human COX-2 enzyme, and Human Peroxiredoxin 5 revealed good binding profiles with the target proteins. The interaction's stability was further assessed using a conventional atomistic 100 ns dynamic simulation study. Hence, our results recommended the rationalized targets 4a, 4b and 4d, to be promising lead candidates for the discovery of novel dual anti-inflammatory and anti-infection agents.http://www.sciencedirect.com/science/article/pii/S18785352220054211,4- and 1,5-disubstituted 1,2,3-triazolesClick chemistryAntimicrobialAntioxidantAnt-inflammatoryIn silico studies |
| spellingShingle | Manel Ben Hammouda Iqrar Ahmad Assia Hamdi Amal Dbeibia Harun Patel Nouha Bouali Walid Sabri Hamadou Karim Hosni Siwar Ghannay Fahad Alminderej Emira Noumi Mejdi Snoussi Kaïss Aouadi Adel Kadri Design, synthesis, biological evaluation and in silico studies of novel 1,2,3-triazole linked benzoxazine-2,4-dione conjugates as potent antimicrobial, antioxidant and anti-inflammatory agents Arabian Journal of Chemistry 1,4- and 1,5-disubstituted 1,2,3-triazoles Click chemistry Antimicrobial Antioxidant Ant-inflammatory In silico studies |
| title | Design, synthesis, biological evaluation and in silico studies of novel 1,2,3-triazole linked benzoxazine-2,4-dione conjugates as potent antimicrobial, antioxidant and anti-inflammatory agents |
| title_full | Design, synthesis, biological evaluation and in silico studies of novel 1,2,3-triazole linked benzoxazine-2,4-dione conjugates as potent antimicrobial, antioxidant and anti-inflammatory agents |
| title_fullStr | Design, synthesis, biological evaluation and in silico studies of novel 1,2,3-triazole linked benzoxazine-2,4-dione conjugates as potent antimicrobial, antioxidant and anti-inflammatory agents |
| title_full_unstemmed | Design, synthesis, biological evaluation and in silico studies of novel 1,2,3-triazole linked benzoxazine-2,4-dione conjugates as potent antimicrobial, antioxidant and anti-inflammatory agents |
| title_short | Design, synthesis, biological evaluation and in silico studies of novel 1,2,3-triazole linked benzoxazine-2,4-dione conjugates as potent antimicrobial, antioxidant and anti-inflammatory agents |
| title_sort | design synthesis biological evaluation and in silico studies of novel 1 2 3 triazole linked benzoxazine 2 4 dione conjugates as potent antimicrobial antioxidant and anti inflammatory agents |
| topic | 1,4- and 1,5-disubstituted 1,2,3-triazoles Click chemistry Antimicrobial Antioxidant Ant-inflammatory In silico studies |
| url | http://www.sciencedirect.com/science/article/pii/S1878535222005421 |
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