Multifunctional Derivatives of Spiropyrrolidine Tethered Indeno-Quinoxaline Heterocyclic Hybrids as Potent Antimicrobial, Antioxidant and Antidiabetic Agents: Design, Synthesis, In Vitro and In Silico Approaches
To combat emerging antimicrobial-resistant microbes, there is an urgent need to develop new antimicrobials with better therapeutic profiles. For this, a series of 13 new spiropyrrolidine derivatives were designed, synthesized, characterized and evaluated for their in vitro antimicrobial, antioxidant...
| الحاوية / القاعدة: | Molecules |
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| المؤلفون الرئيسيون: | , , , , , , , , , , , , , , |
| التنسيق: | مقال |
| اللغة: | الإنجليزية |
| منشور في: |
MDPI AG
2022-10-01
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| الموضوعات: | |
| الوصول للمادة أونلاين: | https://www.mdpi.com/1420-3049/27/21/7248 |
| _version_ | 1851844036042686464 |
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| author | Nouha Bouali Manel Ben Hammouda Iqrar Ahmad Siwar Ghannay Amira Thouri Amal Dbeibia Harun Patel Walid Sabri Hamadou Karim Hosni Mejdi Snoussi Mohd Adnan Md Imtaiyaz Hassan Emira Noumi Kaïss Aouadi Adel Kadri |
| author_facet | Nouha Bouali Manel Ben Hammouda Iqrar Ahmad Siwar Ghannay Amira Thouri Amal Dbeibia Harun Patel Walid Sabri Hamadou Karim Hosni Mejdi Snoussi Mohd Adnan Md Imtaiyaz Hassan Emira Noumi Kaïss Aouadi Adel Kadri |
| author_sort | Nouha Bouali |
| collection | DOAJ |
| container_title | Molecules |
| description | To combat emerging antimicrobial-resistant microbes, there is an urgent need to develop new antimicrobials with better therapeutic profiles. For this, a series of 13 new spiropyrrolidine derivatives were designed, synthesized, characterized and evaluated for their in vitro antimicrobial, antioxidant and antidiabetic potential. Antimicrobial results revealed that the designed compounds displayed good activity against clinical isolated strains, with <b>5d</b> being the most potent (MIC 3.95 mM against <i>Staphylococcus aureus</i> ATCC 25923) compared to tetracycline (MIC 576.01 mM). The antioxidant activity was assessed by trapping DPPH, ABTS and FRAP assays. The results suggest remarkable antioxidant potential of all synthesized compounds, particularly <b>5c</b>, exhibiting the strongest activity with IC<sub>50</sub> of 3.26 ± 0.32 mM (DPPH), 7.03 ± 0.07 mM (ABTS) and 3.69 ± 0.72 mM (FRAP). Tested for their <i>α</i>-amylase inhibitory effect, the examined analogues display a variable degree of <i>α</i>-amylase activity with IC<sub>50</sub> ranging between 0.55 ± 0.38 mM and 2.19 ± 0.23 mM compared to acarbose (IC<sub>50</sub> 1.19 ± 0.02 mM), with the most active compounds being <b>5d</b>, followed by <b>5c</b> and <b>5j</b>, affording IC<sub>50</sub> of 0.55 ± 0.38 mM, 0.92 ± 0.10 mM, and 0.95 ± 0.14 mM, respectively. Preliminary structure–activity relationships revealed the importance of such substituents in enhancing the activity. Furthermore, the ADME screening test was applied to optimize the physicochemical properties and determine their drug-like characteristics. Binding interactions and stability between ligands and active residues of the investigated enzymes were confirmed through molecular docking and dynamic simulation study. These findings provided guidance for further developing leading new spiropyrrolidine scaffolds with improved dual antimicrobial and antidiabetic activities. |
| format | Article |
| id | doaj-art-e8b4b151b7a64fb29a98d0098c9b2167 |
| institution | Directory of Open Access Journals |
| issn | 1420-3049 |
| language | English |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| spelling | doaj-art-e8b4b151b7a64fb29a98d0098c9b21672025-08-19T22:27:05ZengMDPI AGMolecules1420-30492022-10-012721724810.3390/molecules27217248Multifunctional Derivatives of Spiropyrrolidine Tethered Indeno-Quinoxaline Heterocyclic Hybrids as Potent Antimicrobial, Antioxidant and Antidiabetic Agents: Design, Synthesis, In Vitro and In Silico ApproachesNouha Bouali0Manel Ben Hammouda1Iqrar Ahmad2Siwar Ghannay3Amira Thouri4Amal Dbeibia5Harun Patel6Walid Sabri Hamadou7Karim Hosni8Mejdi Snoussi9Mohd Adnan10Md Imtaiyaz Hassan11Emira Noumi12Kaïss Aouadi13Adel Kadri14Department of Biology, College of Science, Hail University, P.O. Box 2440, Hail 2440, Saudi ArabiaLaboratory of Heterocyclic Chemistry Natural Product and Reactivity/CHPNR, Department of Chemistry, Faculty of Science of Monastir, University of Monastir, Monastir 5000, TunisiaDivision of Computer Aided Drug Design, Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur 425405, Maharashtra, IndiaDepartment of Chemistry, College of Science, Qassim University, Buraidah 51452, Saudi ArabiaLaboratory of Bioresources, Biology Integrative and Valorization, Higher Institute of Biotechnology of Monastir, University of Monastir, Monastir 5000, TunisiaLaboratory of Analyzes, Treatment and Valorization of Environmental Pollutants and Products, Faculty of Pharmacy of Monastir, University of Monastir, Monastir 5019, TunisiaDivision of Computer Aided Drug Design, Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur 425405, Maharashtra, IndiaDepartment of Biology, College of Science, Hail University, P.O. Box 2440, Hail 2440, Saudi ArabiaLaboratoire des Substances Naturelles, Institute National de Recherche et d’Analyse Physico-Chimique, Biotechpôle de Sidi Thabet, Sidi Thabet 2020, TunisiaDepartment of Biology, College of Science, Hail University, P.O. Box 2440, Hail 2440, Saudi ArabiaDepartment of Biology, College of Science, Hail University, P.O. Box 2440, Hail 2440, Saudi ArabiaCenter for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, IndiaDepartment of Biology, College of Science, Hail University, P.O. Box 2440, Hail 2440, Saudi ArabiaDepartment of Chemistry, College of Science, Qassim University, Buraidah 51452, Saudi ArabiaDepartment of Chemistry, Faculty of Science and Arts of Baljurashi, Albaha University, Al Bahah P.O. Box 1988, Saudi ArabiaTo combat emerging antimicrobial-resistant microbes, there is an urgent need to develop new antimicrobials with better therapeutic profiles. For this, a series of 13 new spiropyrrolidine derivatives were designed, synthesized, characterized and evaluated for their in vitro antimicrobial, antioxidant and antidiabetic potential. Antimicrobial results revealed that the designed compounds displayed good activity against clinical isolated strains, with <b>5d</b> being the most potent (MIC 3.95 mM against <i>Staphylococcus aureus</i> ATCC 25923) compared to tetracycline (MIC 576.01 mM). The antioxidant activity was assessed by trapping DPPH, ABTS and FRAP assays. The results suggest remarkable antioxidant potential of all synthesized compounds, particularly <b>5c</b>, exhibiting the strongest activity with IC<sub>50</sub> of 3.26 ± 0.32 mM (DPPH), 7.03 ± 0.07 mM (ABTS) and 3.69 ± 0.72 mM (FRAP). Tested for their <i>α</i>-amylase inhibitory effect, the examined analogues display a variable degree of <i>α</i>-amylase activity with IC<sub>50</sub> ranging between 0.55 ± 0.38 mM and 2.19 ± 0.23 mM compared to acarbose (IC<sub>50</sub> 1.19 ± 0.02 mM), with the most active compounds being <b>5d</b>, followed by <b>5c</b> and <b>5j</b>, affording IC<sub>50</sub> of 0.55 ± 0.38 mM, 0.92 ± 0.10 mM, and 0.95 ± 0.14 mM, respectively. Preliminary structure–activity relationships revealed the importance of such substituents in enhancing the activity. Furthermore, the ADME screening test was applied to optimize the physicochemical properties and determine their drug-like characteristics. Binding interactions and stability between ligands and active residues of the investigated enzymes were confirmed through molecular docking and dynamic simulation study. These findings provided guidance for further developing leading new spiropyrrolidine scaffolds with improved dual antimicrobial and antidiabetic activities.https://www.mdpi.com/1420-3049/27/21/7248spiropyrrolidine derivativesantimicrobialantioxidantantidiabeticADMEmolecular docking and dynamic simulation |
| spellingShingle | Nouha Bouali Manel Ben Hammouda Iqrar Ahmad Siwar Ghannay Amira Thouri Amal Dbeibia Harun Patel Walid Sabri Hamadou Karim Hosni Mejdi Snoussi Mohd Adnan Md Imtaiyaz Hassan Emira Noumi Kaïss Aouadi Adel Kadri Multifunctional Derivatives of Spiropyrrolidine Tethered Indeno-Quinoxaline Heterocyclic Hybrids as Potent Antimicrobial, Antioxidant and Antidiabetic Agents: Design, Synthesis, In Vitro and In Silico Approaches spiropyrrolidine derivatives antimicrobial antioxidant antidiabetic ADME molecular docking and dynamic simulation |
| title | Multifunctional Derivatives of Spiropyrrolidine Tethered Indeno-Quinoxaline Heterocyclic Hybrids as Potent Antimicrobial, Antioxidant and Antidiabetic Agents: Design, Synthesis, In Vitro and In Silico Approaches |
| title_full | Multifunctional Derivatives of Spiropyrrolidine Tethered Indeno-Quinoxaline Heterocyclic Hybrids as Potent Antimicrobial, Antioxidant and Antidiabetic Agents: Design, Synthesis, In Vitro and In Silico Approaches |
| title_fullStr | Multifunctional Derivatives of Spiropyrrolidine Tethered Indeno-Quinoxaline Heterocyclic Hybrids as Potent Antimicrobial, Antioxidant and Antidiabetic Agents: Design, Synthesis, In Vitro and In Silico Approaches |
| title_full_unstemmed | Multifunctional Derivatives of Spiropyrrolidine Tethered Indeno-Quinoxaline Heterocyclic Hybrids as Potent Antimicrobial, Antioxidant and Antidiabetic Agents: Design, Synthesis, In Vitro and In Silico Approaches |
| title_short | Multifunctional Derivatives of Spiropyrrolidine Tethered Indeno-Quinoxaline Heterocyclic Hybrids as Potent Antimicrobial, Antioxidant and Antidiabetic Agents: Design, Synthesis, In Vitro and In Silico Approaches |
| title_sort | multifunctional derivatives of spiropyrrolidine tethered indeno quinoxaline heterocyclic hybrids as potent antimicrobial antioxidant and antidiabetic agents design synthesis in vitro and in silico approaches |
| topic | spiropyrrolidine derivatives antimicrobial antioxidant antidiabetic ADME molecular docking and dynamic simulation |
| url | https://www.mdpi.com/1420-3049/27/21/7248 |
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