Towards New Scaffolds for Antimicrobial Activity—In Silico/In Vitro Workflow Introducing New Lead Compounds
<b>Background/Objectives</b>: The rapid evolution of bacterial resistance and the high cost of drug development have attributed greatly to the dearth in drug design. Computational approaches and natural product exploitation offer potential solutions to accelerate drug discovery. <b>...
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| Format: | Article |
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MDPI AG
2024-12-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/14/1/11 |
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| author | Maria Mangana George Lambrinidis Ioannis K. Kostakis Ioanna Kalpaktsi Marina Sagnou Chrysoula Nicolaou Emmanuel Mikros Stylianos Chatzipanagiotou Anastasios Ioannidis |
| author_facet | Maria Mangana George Lambrinidis Ioannis K. Kostakis Ioanna Kalpaktsi Marina Sagnou Chrysoula Nicolaou Emmanuel Mikros Stylianos Chatzipanagiotou Anastasios Ioannidis |
| author_sort | Maria Mangana |
| collection | DOAJ |
| description | <b>Background/Objectives</b>: The rapid evolution of bacterial resistance and the high cost of drug development have attributed greatly to the dearth in drug design. Computational approaches and natural product exploitation offer potential solutions to accelerate drug discovery. <b>Methods</b>: In this research article, we aimed to identify novel antibacterial hits. For the in silico studies, molecular scaffolds from the in-house chemical library of the Department of Pharmacy of Athens (Pharmalab) and the National Cancer Institute (NCI) were screened and selected for further experimental procedures. Compounds from both libraries that were not previously screened for their antimicrobial properties were tested in vitro against Gram-positive and Gram-negative bacterial strains. The microdilution method was used to determine the minimum inhibitory concentrations (MICs). <b>Results</b>: In silico screening identified twenty promising molecules from the NCI and seven from the Pharmalab databases. The unexplored compounds for their antibacterial activity can be characterized as weak strain-specific antimicrobials. The <b>NSC 610491</b> and <b>NSC 610493</b> were active against <i>Staphylococcus aureus</i> (MIC: 25 and 12.5 µg/mL, respectively) and methicillin-resistant <i>S. aureus</i> (MRSA) (MIC: 50 and 12.5 µg/mL, respectively). Six out of seven hydroxytyrosol (HTy) compounds were moderately active (MIC: 25–50 µg/mL) against <i>S. aureus</i>, MRSA and <i>Enterococcus faecalis</i>. For the Gram-negative bacteria, no activity was detected (≥100 µg/mL). <b>Conclusions</b>: The tested scaffolds could be considered as promising candidates for novel antimicrobials with improvements. Further experimentation is required to assess mechanisms of action and evaluate the efficacy and safety. |
| format | Article |
| id | doaj-art-f7d83a59487641709acf0d42ab462469 |
| institution | Kabale University |
| issn | 2079-6382 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj-art-f7d83a59487641709acf0d42ab4624692025-01-24T13:18:31ZengMDPI AGAntibiotics2079-63822024-12-011411110.3390/antibiotics14010011Towards New Scaffolds for Antimicrobial Activity—In Silico/In Vitro Workflow Introducing New Lead CompoundsMaria Mangana0George Lambrinidis1Ioannis K. Kostakis2Ioanna Kalpaktsi3Marina Sagnou4Chrysoula Nicolaou5Emmanuel Mikros6Stylianos Chatzipanagiotou7Anastasios Ioannidis8Department of Clinical Microbiology, Athens Medical School, Aeginition Hospital, 11528 Athens, GreeceDivision of Pharmaceutical Chemistry, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, 15771 Athens, GreeceDivision of Pharmaceutical Chemistry, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, 15771 Athens, GreeceDivision of Pharmaceutical Chemistry, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, 15771 Athens, GreeceInstitute of Biosciences & Application, NCSR “Demokritos”, 15310 Athens, GreeceDepartment of Clinical Microbiology, Athens Medical School, Aeginition Hospital, 11528 Athens, GreeceDivision of Pharmaceutical Chemistry, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, 15771 Athens, GreeceDepartment of Clinical Microbiology, Athens Medical School, Aeginition Hospital, 11528 Athens, GreeceDepartment of Nursing, Faculty of Health Sciences, University of Peloponnese, 22100 Tripolis, Greece<b>Background/Objectives</b>: The rapid evolution of bacterial resistance and the high cost of drug development have attributed greatly to the dearth in drug design. Computational approaches and natural product exploitation offer potential solutions to accelerate drug discovery. <b>Methods</b>: In this research article, we aimed to identify novel antibacterial hits. For the in silico studies, molecular scaffolds from the in-house chemical library of the Department of Pharmacy of Athens (Pharmalab) and the National Cancer Institute (NCI) were screened and selected for further experimental procedures. Compounds from both libraries that were not previously screened for their antimicrobial properties were tested in vitro against Gram-positive and Gram-negative bacterial strains. The microdilution method was used to determine the minimum inhibitory concentrations (MICs). <b>Results</b>: In silico screening identified twenty promising molecules from the NCI and seven from the Pharmalab databases. The unexplored compounds for their antibacterial activity can be characterized as weak strain-specific antimicrobials. The <b>NSC 610491</b> and <b>NSC 610493</b> were active against <i>Staphylococcus aureus</i> (MIC: 25 and 12.5 µg/mL, respectively) and methicillin-resistant <i>S. aureus</i> (MRSA) (MIC: 50 and 12.5 µg/mL, respectively). Six out of seven hydroxytyrosol (HTy) compounds were moderately active (MIC: 25–50 µg/mL) against <i>S. aureus</i>, MRSA and <i>Enterococcus faecalis</i>. For the Gram-negative bacteria, no activity was detected (≥100 µg/mL). <b>Conclusions</b>: The tested scaffolds could be considered as promising candidates for novel antimicrobials with improvements. Further experimentation is required to assess mechanisms of action and evaluate the efficacy and safety.https://www.mdpi.com/2079-6382/14/1/11ligand-based drug designmultidrug-resistant bacteriaantimicrobial activitychemical librarieslead optimization |
| spellingShingle | Maria Mangana George Lambrinidis Ioannis K. Kostakis Ioanna Kalpaktsi Marina Sagnou Chrysoula Nicolaou Emmanuel Mikros Stylianos Chatzipanagiotou Anastasios Ioannidis Towards New Scaffolds for Antimicrobial Activity—In Silico/In Vitro Workflow Introducing New Lead Compounds Antibiotics ligand-based drug design multidrug-resistant bacteria antimicrobial activity chemical libraries lead optimization |
| title | Towards New Scaffolds for Antimicrobial Activity—In Silico/In Vitro Workflow Introducing New Lead Compounds |
| title_full | Towards New Scaffolds for Antimicrobial Activity—In Silico/In Vitro Workflow Introducing New Lead Compounds |
| title_fullStr | Towards New Scaffolds for Antimicrobial Activity—In Silico/In Vitro Workflow Introducing New Lead Compounds |
| title_full_unstemmed | Towards New Scaffolds for Antimicrobial Activity—In Silico/In Vitro Workflow Introducing New Lead Compounds |
| title_short | Towards New Scaffolds for Antimicrobial Activity—In Silico/In Vitro Workflow Introducing New Lead Compounds |
| title_sort | towards new scaffolds for antimicrobial activity in silico in vitro workflow introducing new lead compounds |
| topic | ligand-based drug design multidrug-resistant bacteria antimicrobial activity chemical libraries lead optimization |
| url | https://www.mdpi.com/2079-6382/14/1/11 |
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