The depsidones from marine sponge-derived fungus Aspergillus unguis IB151 as an anti-MRSA agent: Molecular docking, pharmacokinetics analysis, and molecular dynamic simulation studies
Methicillin-resistant Staphylococcus aureus (MRSA) is an emerging nosocomial pathogen among hospitalized patients, with high morbidity and mortality rates. The discovery of a novel antibacterial is urgently needed to address this resistance problem. The present study aims to explore the antibacteria...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Saudi Pharmaceutical Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1319016423002396 |
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| author | Dian Handayani Ibtisamatul Aminah Purnawan Pontana Putra Andani Eka Putra Dayar Arbain Herland Satriawan Mai Efdi Ismail Celik Trina Ekawati Tallei |
| author_facet | Dian Handayani Ibtisamatul Aminah Purnawan Pontana Putra Andani Eka Putra Dayar Arbain Herland Satriawan Mai Efdi Ismail Celik Trina Ekawati Tallei |
| author_sort | Dian Handayani |
| collection | DOAJ |
| description | Methicillin-resistant Staphylococcus aureus (MRSA) is an emerging nosocomial pathogen among hospitalized patients, with high morbidity and mortality rates. The discovery of a novel antibacterial is urgently needed to address this resistance problem. The present study aims to explore the antibacterial potential of three depsidone compounds: 2-clorounguinol (1), unguinol (2), and nidulin (3), isolated from the marine sponge-derived fungus Aspergillus unguis IB1, both in vitro and in silico. The antibacterial activity of all compounds was evaluated by calculating the Minimum inhibitory concentration (MIC) and Minimum bactericidal concentration (MBC) against MRSA using agar diffusion and total plate count methods, respectively. Bacterial cell morphology changes were studied for the first time using scanning electron microscopy (SEM). Molecular docking, pharmacokinetics analysis, and molecular dynamics simulation were performed to determine possible protein–ligand interactions and the stability of the targeting penicillin-binding protein 2a (PBP2a) against 2-clorounguinol (1). The research findings indicated that compounds 1 to 3 exhibited MIC and MBC values of 2 µg/mL and 16 µg/mL against MRSA, respectively. MRSA cells displayed a distinct shape after the addition of the depsidone compound, as observed in SEM. According to the in silico study, 2-chlorounguinol exhibited the highest binding-free energy (BFE) with PBP2a (-6.7 kcal/mol). For comparison, (E)-3-(2-(4-cyanostyryl)-4-oxoquinazolin-3(4H)-yl) benzoic acid inhibits PBP2a with a BFE less than −6.6 kcal/mol. Based on the Lipinski's rule of 5, depsidone compounds constitute a class of compounds with good pharmacokinetic properties, being easily absorbed and permeable. These findings suggest that 2-chlorounguinol possesses potential antibacterial activity and could be developed as an antibiotic adjuvant to reduce antimicrobial resistance. |
| first_indexed | 2024-03-12T01:47:28Z |
| format | Article |
| id | doaj.art-742a21db6d004451a5783e7df8d761bd |
| institution | Directory Open Access Journal |
| issn | 1319-0164 |
| language | English |
| last_indexed | 2024-03-12T01:47:28Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Saudi Pharmaceutical Journal |
| spelling | doaj.art-742a21db6d004451a5783e7df8d761bd2023-09-09T04:54:46ZengElsevierSaudi Pharmaceutical Journal1319-01642023-09-01319101744The depsidones from marine sponge-derived fungus Aspergillus unguis IB151 as an anti-MRSA agent: Molecular docking, pharmacokinetics analysis, and molecular dynamic simulation studiesDian Handayani0Ibtisamatul Aminah1Purnawan Pontana Putra2Andani Eka Putra3Dayar Arbain4Herland Satriawan5Mai Efdi6Ismail Celik7Trina Ekawati Tallei8Faculty of Pharmacy/Sumatran Biota Laboratory, Andalas University, Padang 25163, Indonesia; Corresponding author.Faculty of Pharmacy/Sumatran Biota Laboratory, Andalas University, Padang 25163, Indonesia; Department of Biomedical Science, Faculty of Medicine, Andalas University, Padang 25163, IndonesiaFaculty of Pharmacy/Sumatran Biota Laboratory, Andalas University, Padang 25163, IndonesiaDepartment of Biomedical Science, Faculty of Medicine, Andalas University, Padang 25163, IndonesiaFaculty of Pharmacy, 17 Agustus 1945 University, Sunter Permai Raya St, Jakarta 14350, IndonesiaInstitute of Ocean and Earth Sciences, University of Malaya, 50603, Kuala Lumpur, MalaysiaDepartment of Chemistry, Faculty of Mathematics and Natural Sciences, Andalas University, Padang 25163, IndonesiaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Erciyes University, Kayseri 38039, TurkeyDepartment of Biology, Faculty of Mathematics and Natural Sciences, Sam Ratulangi University, Manado 95115, IndonesiaMethicillin-resistant Staphylococcus aureus (MRSA) is an emerging nosocomial pathogen among hospitalized patients, with high morbidity and mortality rates. The discovery of a novel antibacterial is urgently needed to address this resistance problem. The present study aims to explore the antibacterial potential of three depsidone compounds: 2-clorounguinol (1), unguinol (2), and nidulin (3), isolated from the marine sponge-derived fungus Aspergillus unguis IB1, both in vitro and in silico. The antibacterial activity of all compounds was evaluated by calculating the Minimum inhibitory concentration (MIC) and Minimum bactericidal concentration (MBC) against MRSA using agar diffusion and total plate count methods, respectively. Bacterial cell morphology changes were studied for the first time using scanning electron microscopy (SEM). Molecular docking, pharmacokinetics analysis, and molecular dynamics simulation were performed to determine possible protein–ligand interactions and the stability of the targeting penicillin-binding protein 2a (PBP2a) against 2-clorounguinol (1). The research findings indicated that compounds 1 to 3 exhibited MIC and MBC values of 2 µg/mL and 16 µg/mL against MRSA, respectively. MRSA cells displayed a distinct shape after the addition of the depsidone compound, as observed in SEM. According to the in silico study, 2-chlorounguinol exhibited the highest binding-free energy (BFE) with PBP2a (-6.7 kcal/mol). For comparison, (E)-3-(2-(4-cyanostyryl)-4-oxoquinazolin-3(4H)-yl) benzoic acid inhibits PBP2a with a BFE less than −6.6 kcal/mol. Based on the Lipinski's rule of 5, depsidone compounds constitute a class of compounds with good pharmacokinetic properties, being easily absorbed and permeable. These findings suggest that 2-chlorounguinol possesses potential antibacterial activity and could be developed as an antibiotic adjuvant to reduce antimicrobial resistance.http://www.sciencedirect.com/science/article/pii/S1319016423002396DepsidoneMICMBCPBP2aMolecular dockingMolecular dynamics simulations |
| spellingShingle | Dian Handayani Ibtisamatul Aminah Purnawan Pontana Putra Andani Eka Putra Dayar Arbain Herland Satriawan Mai Efdi Ismail Celik Trina Ekawati Tallei The depsidones from marine sponge-derived fungus Aspergillus unguis IB151 as an anti-MRSA agent: Molecular docking, pharmacokinetics analysis, and molecular dynamic simulation studies Saudi Pharmaceutical Journal Depsidone MIC MBC PBP2a Molecular docking Molecular dynamics simulations |
| title | The depsidones from marine sponge-derived fungus Aspergillus unguis IB151 as an anti-MRSA agent: Molecular docking, pharmacokinetics analysis, and molecular dynamic simulation studies |
| title_full | The depsidones from marine sponge-derived fungus Aspergillus unguis IB151 as an anti-MRSA agent: Molecular docking, pharmacokinetics analysis, and molecular dynamic simulation studies |
| title_fullStr | The depsidones from marine sponge-derived fungus Aspergillus unguis IB151 as an anti-MRSA agent: Molecular docking, pharmacokinetics analysis, and molecular dynamic simulation studies |
| title_full_unstemmed | The depsidones from marine sponge-derived fungus Aspergillus unguis IB151 as an anti-MRSA agent: Molecular docking, pharmacokinetics analysis, and molecular dynamic simulation studies |
| title_short | The depsidones from marine sponge-derived fungus Aspergillus unguis IB151 as an anti-MRSA agent: Molecular docking, pharmacokinetics analysis, and molecular dynamic simulation studies |
| title_sort | depsidones from marine sponge derived fungus aspergillus unguis ib151 as an anti mrsa agent molecular docking pharmacokinetics analysis and molecular dynamic simulation studies |
| topic | Depsidone MIC MBC PBP2a Molecular docking Molecular dynamics simulations |
| url | http://www.sciencedirect.com/science/article/pii/S1319016423002396 |
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