Fighting Antibiotic Resistance: New Pyrimidine-Clubbed Benzimidazole Derivatives as Potential DHFR Inhibitors
The present work describes the design and development of seventeen pyrimidine-clubbed benzimidazole derivatives as potential dihydrofolate reductase (DHFR) inhibitors. These compounds were filtered by using ADMET, drug-likeness characteristics calculations, and molecular docking experiments. Compoun...
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| Format: | Article |
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MDPI AG
2023-01-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/2/501 |
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| author | M. Akiful Haque Akash Marathakam Ritesh Rana Samar J Almehmadi Vishal B. Tambe Manoj S. Charde Fahadul Islam Falak A. Siddiqui Giulia Culletta Anna Maria Almerico Marco Tutone Sharuk L. Khan |
| author_facet | M. Akiful Haque Akash Marathakam Ritesh Rana Samar J Almehmadi Vishal B. Tambe Manoj S. Charde Fahadul Islam Falak A. Siddiqui Giulia Culletta Anna Maria Almerico Marco Tutone Sharuk L. Khan |
| author_sort | M. Akiful Haque |
| collection | DOAJ |
| description | The present work describes the design and development of seventeen pyrimidine-clubbed benzimidazole derivatives as potential dihydrofolate reductase (DHFR) inhibitors. These compounds were filtered by using ADMET, drug-likeness characteristics calculations, and molecular docking experiments. Compounds <b>27</b>, <b>29</b>, <b>30</b>, <b>33</b>, <b>37</b>, <b>38</b>, and <b>41</b> were chosen for the synthesis based on the results of the in silico screening. Each of the synthesized compounds was tested for its in vitro antibacterial and antifungal activities using a variety of strains. All the compounds showed antibacterial properties against Gram-positive bacteria (<i>Staphylococcus aureus</i> and <i>Staphylococcus pyogenes</i>) as well as Gram-negative bacteria (<i>Escherichia coli</i> and <i>Pseudomonas aeruginosa</i>). Most of the compounds either had a higher potency than chloramphenicol or an equivalent potency to ciprofloxacin. Compounds <b>29</b> and <b>33</b> were effective against all the bacterial and fungal strains. Finally, the 1,2,3,4-tetrahydropyrimidine-2-thiol derivatives with a 6-chloro-2-(chloromethyl)-1<i>H</i>-benzo[<i>d</i>]imidazole moiety are potent enough to be considered a promising lead for the discovery of an effective antibacterial agent. |
| first_indexed | 2024-03-09T11:36:57Z |
| format | Article |
| id | doaj.art-6190939685294e0bb355a7bcdf6a987b |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T11:36:57Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-6190939685294e0bb355a7bcdf6a987b2023-11-30T23:40:44ZengMDPI AGMolecules1420-30492023-01-0128250110.3390/molecules28020501Fighting Antibiotic Resistance: New Pyrimidine-Clubbed Benzimidazole Derivatives as Potential DHFR InhibitorsM. Akiful Haque0Akash Marathakam1Ritesh Rana2Samar J Almehmadi3Vishal B. Tambe4Manoj S. Charde5Fahadul Islam6Falak A. Siddiqui7Giulia Culletta8Anna Maria Almerico9Marco Tutone10Sharuk L. Khan11Department of Pharmaceutical Analysis, School of Pharmacy, Anurag University, Ghatkesar, Hyderabad 500088, IndiaNational College of Pharmacy, Kozhikode 673602, IndiaDepartment of Pharmaceutics, Himachal Institute of Pharmaceutical Education and Research (HIPER), Bela, Nadaun, Hamirpur 177042, IndiaDepartment of Chemistry, Faculty of Applied Science, Umm-Al-Qura University, Makkah 24382, Saudi ArabiaDepartment of Pharmaceutical Chemistry, Pravara Rural College of Pharmacy, Loni 413736, IndiaDepartment of Pharmaceutical Chemistry, Government College of Pharmacy, Karad 415124, IndiaDepartment of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, BangladeshDepartment of Pharmaceutical Chemistry, N.B.S. Institute of Pharmacy, Ausa 413520, IndiaDipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, Università degli Studi di Palermo, 90123 Palermo, ItalyDipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, Università degli Studi di Palermo, 90123 Palermo, ItalyDipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, Università degli Studi di Palermo, 90123 Palermo, ItalyDepartment of Pharmaceutical Chemistry, N.B.S. Institute of Pharmacy, Ausa 413520, IndiaThe present work describes the design and development of seventeen pyrimidine-clubbed benzimidazole derivatives as potential dihydrofolate reductase (DHFR) inhibitors. These compounds were filtered by using ADMET, drug-likeness characteristics calculations, and molecular docking experiments. Compounds <b>27</b>, <b>29</b>, <b>30</b>, <b>33</b>, <b>37</b>, <b>38</b>, and <b>41</b> were chosen for the synthesis based on the results of the in silico screening. Each of the synthesized compounds was tested for its in vitro antibacterial and antifungal activities using a variety of strains. All the compounds showed antibacterial properties against Gram-positive bacteria (<i>Staphylococcus aureus</i> and <i>Staphylococcus pyogenes</i>) as well as Gram-negative bacteria (<i>Escherichia coli</i> and <i>Pseudomonas aeruginosa</i>). Most of the compounds either had a higher potency than chloramphenicol or an equivalent potency to ciprofloxacin. Compounds <b>29</b> and <b>33</b> were effective against all the bacterial and fungal strains. Finally, the 1,2,3,4-tetrahydropyrimidine-2-thiol derivatives with a 6-chloro-2-(chloromethyl)-1<i>H</i>-benzo[<i>d</i>]imidazole moiety are potent enough to be considered a promising lead for the discovery of an effective antibacterial agent.https://www.mdpi.com/1420-3049/28/2/501DHFRantifungalantibacterialpyrimidinesbenzimidazolesADMETlab 2.0 |
| spellingShingle | M. Akiful Haque Akash Marathakam Ritesh Rana Samar J Almehmadi Vishal B. Tambe Manoj S. Charde Fahadul Islam Falak A. Siddiqui Giulia Culletta Anna Maria Almerico Marco Tutone Sharuk L. Khan Fighting Antibiotic Resistance: New Pyrimidine-Clubbed Benzimidazole Derivatives as Potential DHFR Inhibitors Molecules DHFR antifungal antibacterial pyrimidines benzimidazoles ADMETlab 2.0 |
| title | Fighting Antibiotic Resistance: New Pyrimidine-Clubbed Benzimidazole Derivatives as Potential DHFR Inhibitors |
| title_full | Fighting Antibiotic Resistance: New Pyrimidine-Clubbed Benzimidazole Derivatives as Potential DHFR Inhibitors |
| title_fullStr | Fighting Antibiotic Resistance: New Pyrimidine-Clubbed Benzimidazole Derivatives as Potential DHFR Inhibitors |
| title_full_unstemmed | Fighting Antibiotic Resistance: New Pyrimidine-Clubbed Benzimidazole Derivatives as Potential DHFR Inhibitors |
| title_short | Fighting Antibiotic Resistance: New Pyrimidine-Clubbed Benzimidazole Derivatives as Potential DHFR Inhibitors |
| title_sort | fighting antibiotic resistance new pyrimidine clubbed benzimidazole derivatives as potential dhfr inhibitors |
| topic | DHFR antifungal antibacterial pyrimidines benzimidazoles ADMETlab 2.0 |
| url | https://www.mdpi.com/1420-3049/28/2/501 |
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