Multi-Target In Silico Evaluation of New 2-Pyrazolines as Antimicrobial Agents
The world today is being ravaged by the emergence and re-emergence of microbial infections caused by antimicrobial-resistant strains, brought about primarily by the frequent and perhaps unnecessary use of antimicrobial agents. A need therefore arises to develop new antimicrobial drugs that can comba...
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MDPI AG
2025-03-01
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| Online Access: | https://www.mdpi.com/2673-4583/16/1/110 |
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| author | Zukhruf Salami Asmau Hamza Abdullahi Idris Yusuf Jimoh |
| author_facet | Zukhruf Salami Asmau Hamza Abdullahi Idris Yusuf Jimoh |
| author_sort | Zukhruf Salami |
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| description | The world today is being ravaged by the emergence and re-emergence of microbial infections caused by antimicrobial-resistant strains, brought about primarily by the frequent and perhaps unnecessary use of antimicrobial agents. A need therefore arises to develop new antimicrobial drugs that can combat these pathogens resistant to currently available antibiotics. This present study has adopted a multi-enzyme in silico approach in evaluating new 2-pyrazolines as antimicrobial agents, targeting and aiming to inhibit three pivotal enzymes in the bacteria’s life cycle. A library of 2-pyrazolines was tailored to achieve the desired activity. The library of compounds and amoxicillin, a standard antimicrobial drug, were docked into the molecular target enzymes. They were also subjected to toxicity and drug-likeness tests, using PROTOX and swissADME, respectively. A moderate toxicity profile was indicated, as more than 90% of the ligands were in ProTox class 4. The majority exhibited advantageous ADME characteristics. A significant number of them demonstrated a binding affinity for the target proteins that was stronger than both the native ligand and the binding affinity of amoxicillin. Ligands 30, 20, and 8 are the notable ones across all target enzymes. These results suggest that these novel ligands may be powerful inhibitors, particularly when it comes to interfering with the formation of bacterial cell walls, folic acid, and nucleotide metabolism. Additional in vivo and in vitro research is required to confirm these results and evaluate their therapeutic potential. |
| format | Article |
| id | doaj-art-e017a23b55db4f23b9d05a4ad4e408a2 |
| institution | Kabale University |
| issn | 2673-4583 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
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| series | Chemistry Proceedings |
| spelling | doaj-art-e017a23b55db4f23b9d05a4ad4e408a22025-08-20T03:27:21ZengMDPI AGChemistry Proceedings2673-45832025-03-0116111010.3390/ecsoc-28-20226Multi-Target In Silico Evaluation of New 2-Pyrazolines as Antimicrobial AgentsZukhruf Salami0Asmau Hamza1Abdullahi Idris2Yusuf Jimoh3Pharmaceutical and Medicinal Chemistry Department, Ahmadu Bello University, Zaria 810107, NigeriaPharmaceutical and Medicinal Chemistry Department, Ahmadu Bello University, Zaria 810107, NigeriaPharmaceutical and Medicinal Chemistry Department, Ahmadu Bello University, Zaria 810107, NigeriaPharmaceutical and Medicinal Chemistry Department, Ahmadu Bello University, Zaria 810107, NigeriaThe world today is being ravaged by the emergence and re-emergence of microbial infections caused by antimicrobial-resistant strains, brought about primarily by the frequent and perhaps unnecessary use of antimicrobial agents. A need therefore arises to develop new antimicrobial drugs that can combat these pathogens resistant to currently available antibiotics. This present study has adopted a multi-enzyme in silico approach in evaluating new 2-pyrazolines as antimicrobial agents, targeting and aiming to inhibit three pivotal enzymes in the bacteria’s life cycle. A library of 2-pyrazolines was tailored to achieve the desired activity. The library of compounds and amoxicillin, a standard antimicrobial drug, were docked into the molecular target enzymes. They were also subjected to toxicity and drug-likeness tests, using PROTOX and swissADME, respectively. A moderate toxicity profile was indicated, as more than 90% of the ligands were in ProTox class 4. The majority exhibited advantageous ADME characteristics. A significant number of them demonstrated a binding affinity for the target proteins that was stronger than both the native ligand and the binding affinity of amoxicillin. Ligands 30, 20, and 8 are the notable ones across all target enzymes. These results suggest that these novel ligands may be powerful inhibitors, particularly when it comes to interfering with the formation of bacterial cell walls, folic acid, and nucleotide metabolism. Additional in vivo and in vitro research is required to confirm these results and evaluate their therapeutic potential.https://www.mdpi.com/2673-4583/16/1/1102-pyrazolinesmulti-targetantimicrobial agentsantimicrobial resistance |
| spellingShingle | Zukhruf Salami Asmau Hamza Abdullahi Idris Yusuf Jimoh Multi-Target In Silico Evaluation of New 2-Pyrazolines as Antimicrobial Agents Chemistry Proceedings 2-pyrazolines multi-target antimicrobial agents antimicrobial resistance |
| title | Multi-Target In Silico Evaluation of New 2-Pyrazolines as Antimicrobial Agents |
| title_full | Multi-Target In Silico Evaluation of New 2-Pyrazolines as Antimicrobial Agents |
| title_fullStr | Multi-Target In Silico Evaluation of New 2-Pyrazolines as Antimicrobial Agents |
| title_full_unstemmed | Multi-Target In Silico Evaluation of New 2-Pyrazolines as Antimicrobial Agents |
| title_short | Multi-Target In Silico Evaluation of New 2-Pyrazolines as Antimicrobial Agents |
| title_sort | multi target in silico evaluation of new 2 pyrazolines as antimicrobial agents |
| topic | 2-pyrazolines multi-target antimicrobial agents antimicrobial resistance |
| url | https://www.mdpi.com/2673-4583/16/1/110 |
| work_keys_str_mv | AT zukhrufsalami multitargetinsilicoevaluationofnew2pyrazolinesasantimicrobialagents AT asmauhamza multitargetinsilicoevaluationofnew2pyrazolinesasantimicrobialagents AT abdullahiidris multitargetinsilicoevaluationofnew2pyrazolinesasantimicrobialagents AT yusufjimoh multitargetinsilicoevaluationofnew2pyrazolinesasantimicrobialagents |