In vitro and in silico antibacterial evaluation of nitrocatechol chalcone and pyrazoline derivatives
The aim of this study was to determine the in vitro antibacterial activity of nitrocatechol chalcone and pyrazoline derivatives previously synthesised by our research group against Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii and Klebsiella aerogenes, and to create and valid...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Results in Chemistry |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211715623004332 |
| _version_ | 1797398621100965888 |
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| author | Alize Hoepfner Anél Petzer Jacobus P. Petzer Judey Pretorius Theunis T. Cloete |
| author_facet | Alize Hoepfner Anél Petzer Jacobus P. Petzer Judey Pretorius Theunis T. Cloete |
| author_sort | Alize Hoepfner |
| collection | DOAJ |
| description | The aim of this study was to determine the in vitro antibacterial activity of nitrocatechol chalcone and pyrazoline derivatives previously synthesised by our research group against Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii and Klebsiella aerogenes, and to create and validate a pharmacophore model using this data. The enrichment factor (EF10%) and the area under the receiver operating characteristic (ROC-AUC) curve were used to validate the pharmacophore model. Using the validated pharmacophore model novel derivatives were designed and synthesised, whereafter the in vitro antibacterial activity of these derivatives was also determined against the susceptible bacteria. After the initial screening, the derivatives only had activity against S. aureus, with compound 2a, 2b and 1b (1–2 µg/ml) having comparable activity to tetracycline (2 µg/ml). A common feature pharmacophore model (max. fit: 4, rank score: 84.02) was able to accurately identify active nitrocatechol chalcones and pyrazoline derivatives within a decoy test set. The best performing pharmacophore model, i.e., hypothesis 9 (EF10%: 6.7, ROC-AUC: 0.85 ± 0.00) indicated that four hydrogen bond acceptors are important for antibacterial activity. This model was used to guide the design and synthesis of novel nitrocatechol chalcone and pyrazoline derivatives of which the in vitro antibacterial activity against both the susceptible and resistant S. aureus strains were determined. The most active compounds were 3i (0.5 µg/ml) and 3c (0.5 µg/ml) against the susceptible and resistant strain respectively, which were more active than tetracycline. |
| first_indexed | 2024-03-09T01:28:12Z |
| format | Article |
| id | doaj.art-5813dcfe787e4618955b4d20fbadb134 |
| institution | Directory Open Access Journal |
| issn | 2211-7156 |
| language | English |
| last_indexed | 2024-03-09T01:28:12Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Results in Chemistry |
| spelling | doaj.art-5813dcfe787e4618955b4d20fbadb1342023-12-10T06:15:34ZengElsevierResults in Chemistry2211-71562023-12-016101194In vitro and in silico antibacterial evaluation of nitrocatechol chalcone and pyrazoline derivativesAlize Hoepfner0Anél Petzer1Jacobus P. Petzer2Judey Pretorius3Theunis T. Cloete4Pharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520, South AfricaPharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa; Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520, South AfricaPharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa; Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520, South AfricaBiomedical Emporium, The Willows Office Park, Unit F2, Corner Simon Vermooten and Farm Roads, Pretoria 0084, South AfricaPharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa; Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa; Corresponding author at: Pharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa.The aim of this study was to determine the in vitro antibacterial activity of nitrocatechol chalcone and pyrazoline derivatives previously synthesised by our research group against Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii and Klebsiella aerogenes, and to create and validate a pharmacophore model using this data. The enrichment factor (EF10%) and the area under the receiver operating characteristic (ROC-AUC) curve were used to validate the pharmacophore model. Using the validated pharmacophore model novel derivatives were designed and synthesised, whereafter the in vitro antibacterial activity of these derivatives was also determined against the susceptible bacteria. After the initial screening, the derivatives only had activity against S. aureus, with compound 2a, 2b and 1b (1–2 µg/ml) having comparable activity to tetracycline (2 µg/ml). A common feature pharmacophore model (max. fit: 4, rank score: 84.02) was able to accurately identify active nitrocatechol chalcones and pyrazoline derivatives within a decoy test set. The best performing pharmacophore model, i.e., hypothesis 9 (EF10%: 6.7, ROC-AUC: 0.85 ± 0.00) indicated that four hydrogen bond acceptors are important for antibacterial activity. This model was used to guide the design and synthesis of novel nitrocatechol chalcone and pyrazoline derivatives of which the in vitro antibacterial activity against both the susceptible and resistant S. aureus strains were determined. The most active compounds were 3i (0.5 µg/ml) and 3c (0.5 µg/ml) against the susceptible and resistant strain respectively, which were more active than tetracycline.http://www.sciencedirect.com/science/article/pii/S2211715623004332Drug repurposingNitrocatecholChalconePyrazolineAntibacterial activityCommon feature pharmacophore modelling |
| spellingShingle | Alize Hoepfner Anél Petzer Jacobus P. Petzer Judey Pretorius Theunis T. Cloete In vitro and in silico antibacterial evaluation of nitrocatechol chalcone and pyrazoline derivatives Results in Chemistry Drug repurposing Nitrocatechol Chalcone Pyrazoline Antibacterial activity Common feature pharmacophore modelling |
| title | In vitro and in silico antibacterial evaluation of nitrocatechol chalcone and pyrazoline derivatives |
| title_full | In vitro and in silico antibacterial evaluation of nitrocatechol chalcone and pyrazoline derivatives |
| title_fullStr | In vitro and in silico antibacterial evaluation of nitrocatechol chalcone and pyrazoline derivatives |
| title_full_unstemmed | In vitro and in silico antibacterial evaluation of nitrocatechol chalcone and pyrazoline derivatives |
| title_short | In vitro and in silico antibacterial evaluation of nitrocatechol chalcone and pyrazoline derivatives |
| title_sort | in vitro and in silico antibacterial evaluation of nitrocatechol chalcone and pyrazoline derivatives |
| topic | Drug repurposing Nitrocatechol Chalcone Pyrazoline Antibacterial activity Common feature pharmacophore modelling |
| url | http://www.sciencedirect.com/science/article/pii/S2211715623004332 |
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