Green Synthesis, Characterization, and Biological Activity of 4-Aminoquinoline Derivatives: Exploring Antibacterial Efficacy, MRSA Inhibition, and PBP2a Docking Insights
A series of 4-aminoquinoline derivatives were prepared using a microwave-assisted method. The reactions were initially carried out on a small scale and subsequently scaled up using a sealed tube. Heating the reactions to 90–150 °C for 90–120 minutes obtained products with up to 95% yields. Structura...
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2025-04-01
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| author | Lo’ay A. Al-Momani Ula A. Abu Shawar Ayman H. Abu Sarhan Rand Shahin Panayiotis A. Koutentis Mohammad K. Abu-Sini Nada J. Mohammad |
| author_facet | Lo’ay A. Al-Momani Ula A. Abu Shawar Ayman H. Abu Sarhan Rand Shahin Panayiotis A. Koutentis Mohammad K. Abu-Sini Nada J. Mohammad |
| author_sort | Lo’ay A. Al-Momani |
| collection | DOAJ |
| description | A series of 4-aminoquinoline derivatives were prepared using a microwave-assisted method. The reactions were initially carried out on a small scale and subsequently scaled up using a sealed tube. Heating the reactions to 90–150 °C for 90–120 minutes obtained products with up to 95% yields. Structural analysis and characterization were achieved using FT-IR, <sup>1</sup>H- and <sup>13</sup>C-NMR spectroscopy and HR-MS. Four compounds displayed low-to-moderate antibacterial activity, with 6-chlorocyclopentaquinolinamine (<b>7b</b>) exhibiting potent inhibition against MRSA (MIC = 0.125 mM) and 2-fluorocycloheptaquinolinamine (<b>9d</b>) showing activity against <i>S. pyogenes</i> (MIC = 0.25 mM). Structure–activity relationship (SAR) docking studies within the Penicillin Binding Protein (PBP2a) binding site (PDB: 4DK1) showed that compounds <b>7b</b> and <b>5b</b> (7-chlorophenylquinolinamine) bind through hydrophobic interactions (ALA601, ILE614), hydrogen bonding (GLN521), and halogen contacts (TYR519, THR399). Compound <b>7b</b> demonstrated enhanced MRSA inhibition due to additional π-alkyl interactions and optimal docking parameters. Conversely, the bulky structure of <b>9d</b> may explain its weaker activity as it likely hindered binding to the target site. This paper highlights the role of structural features in antibacterial efficacy and guides the future optimization of 4-aminoquinoline derivatives. |
| format | Article |
| id | doaj-art-e2a4c5ce6d144e62b81962f92cdbb8f5 |
| institution | Kabale University |
| issn | 2624-8549 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Chemistry |
| spelling | doaj-art-e2a4c5ce6d144e62b81962f92cdbb8f52025-08-20T03:27:29ZengMDPI AGChemistry2624-85492025-04-01737110.3390/chemistry7030071Green Synthesis, Characterization, and Biological Activity of 4-Aminoquinoline Derivatives: Exploring Antibacterial Efficacy, MRSA Inhibition, and PBP2a Docking InsightsLo’ay A. Al-Momani0Ula A. Abu Shawar1Ayman H. Abu Sarhan2Rand Shahin3Panayiotis A. Koutentis4Mohammad K. Abu-Sini5Nada J. Mohammad6Department of Chemistry, Faculty of Science, The Hashemite University, P.O. Box 330127, Zarqa 13133, JordanDepartment of Chemistry, Faculty of Science, The Hashemite University, P.O. Box 330127, Zarqa 13133, JordanDepartment of Chemistry, Faculty of Science, The Hashemite University, P.O. Box 330127, Zarqa 13133, JordanDepartment of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, The Hashemite University, P.O. Box 330127, Zarqa 13133, JordanDepartment of Chemistry, University of Cyprus, P.O. Box 20537, 1678 Nicosia, CyprusDepartment of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman 11733, JordanDepartment of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman 11733, JordanA series of 4-aminoquinoline derivatives were prepared using a microwave-assisted method. The reactions were initially carried out on a small scale and subsequently scaled up using a sealed tube. Heating the reactions to 90–150 °C for 90–120 minutes obtained products with up to 95% yields. Structural analysis and characterization were achieved using FT-IR, <sup>1</sup>H- and <sup>13</sup>C-NMR spectroscopy and HR-MS. Four compounds displayed low-to-moderate antibacterial activity, with 6-chlorocyclopentaquinolinamine (<b>7b</b>) exhibiting potent inhibition against MRSA (MIC = 0.125 mM) and 2-fluorocycloheptaquinolinamine (<b>9d</b>) showing activity against <i>S. pyogenes</i> (MIC = 0.25 mM). Structure–activity relationship (SAR) docking studies within the Penicillin Binding Protein (PBP2a) binding site (PDB: 4DK1) showed that compounds <b>7b</b> and <b>5b</b> (7-chlorophenylquinolinamine) bind through hydrophobic interactions (ALA601, ILE614), hydrogen bonding (GLN521), and halogen contacts (TYR519, THR399). Compound <b>7b</b> demonstrated enhanced MRSA inhibition due to additional π-alkyl interactions and optimal docking parameters. Conversely, the bulky structure of <b>9d</b> may explain its weaker activity as it likely hindered binding to the target site. This paper highlights the role of structural features in antibacterial efficacy and guides the future optimization of 4-aminoquinoline derivatives.https://www.mdpi.com/2624-8549/7/3/71green synthesismicrowave-assisted synthesis4-aminoquinoline derivatives |
| spellingShingle | Lo’ay A. Al-Momani Ula A. Abu Shawar Ayman H. Abu Sarhan Rand Shahin Panayiotis A. Koutentis Mohammad K. Abu-Sini Nada J. Mohammad Green Synthesis, Characterization, and Biological Activity of 4-Aminoquinoline Derivatives: Exploring Antibacterial Efficacy, MRSA Inhibition, and PBP2a Docking Insights Chemistry green synthesis microwave-assisted synthesis 4-aminoquinoline derivatives |
| title | Green Synthesis, Characterization, and Biological Activity of 4-Aminoquinoline Derivatives: Exploring Antibacterial Efficacy, MRSA Inhibition, and PBP2a Docking Insights |
| title_full | Green Synthesis, Characterization, and Biological Activity of 4-Aminoquinoline Derivatives: Exploring Antibacterial Efficacy, MRSA Inhibition, and PBP2a Docking Insights |
| title_fullStr | Green Synthesis, Characterization, and Biological Activity of 4-Aminoquinoline Derivatives: Exploring Antibacterial Efficacy, MRSA Inhibition, and PBP2a Docking Insights |
| title_full_unstemmed | Green Synthesis, Characterization, and Biological Activity of 4-Aminoquinoline Derivatives: Exploring Antibacterial Efficacy, MRSA Inhibition, and PBP2a Docking Insights |
| title_short | Green Synthesis, Characterization, and Biological Activity of 4-Aminoquinoline Derivatives: Exploring Antibacterial Efficacy, MRSA Inhibition, and PBP2a Docking Insights |
| title_sort | green synthesis characterization and biological activity of 4 aminoquinoline derivatives exploring antibacterial efficacy mrsa inhibition and pbp2a docking insights |
| topic | green synthesis microwave-assisted synthesis 4-aminoquinoline derivatives |
| url | https://www.mdpi.com/2624-8549/7/3/71 |
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