In Vitro and In Silico Approaches for the Evaluation of Antimicrobial Activity, Time-Kill Kinetics, and Anti-Biofilm Potential of Thymoquinone (2-Methyl-5-propan-2-ylcyclohexa-2,5-diene-1,4-dione) against Selected Human Pathogens
Thymoquinone (2-methyl-5-propan-2-ylcyclohexa-2,5-diene-1,4-dione; TQ), a principal bioactive phytoconstituent of <i>Nigella sativa</i> essential oil, has been reported to have high antimicrobial potential. Thus, the current study evaluated TQ’s antimicrobial potential against a range of...
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MDPI AG
2022-01-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/11/1/79 |
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| author | Kamal A. Qureshi Mahrukh Imtiaz Adil Parvez Pankaj K. Rai Mariusz Jaremko Abdul-Hamid Emwas Avinash D. Bholay Muhammad Qaiser Fatmi |
| author_facet | Kamal A. Qureshi Mahrukh Imtiaz Adil Parvez Pankaj K. Rai Mariusz Jaremko Abdul-Hamid Emwas Avinash D. Bholay Muhammad Qaiser Fatmi |
| author_sort | Kamal A. Qureshi |
| collection | DOAJ |
| description | Thymoquinone (2-methyl-5-propan-2-ylcyclohexa-2,5-diene-1,4-dione; TQ), a principal bioactive phytoconstituent of <i>Nigella sativa</i> essential oil, has been reported to have high antimicrobial potential. Thus, the current study evaluated TQ’s antimicrobial potential against a range of selected human pathogens using in vitro assays, including time-kill kinetics and anti-biofilm activity. In silico molecular docking of TQ against several antimicrobial target proteins and a detailed intermolecular interaction analysis was performed, including binding energies and docking feasibility. Of the tested bacteria and fungi, <i>S. epidermidis</i> ATCC 12228 and <i>Candida albicans</i> ATCC 10231 were the most susceptible to TQ, with 50.3 ± 0.3 mm and 21.1 ± 0.1 mm zones of inhibition, respectively. Minimum inhibitory concentration (MIC) values of TQ are in the range of 12.5–50 µg/mL, while minimum biocidal concentration (MBC) values are in the range of 25–100 µg/mL against the tested organisms. Time-kill kinetics of TQ revealed that the killing time for the tested bacteria is in the range of 1–6 h with the MBC of TQ. Anti-biofilm activity results demonstrate that the minimum biofilm inhibitory concentration (MBIC) values of TQ are in the range of 25–50 µg/mL, while the minimum biofilm eradication concentration (MBEC) values are in the range of 25–100 µg/mL, for the tested bacteria. In silico molecular docking studies revealed four preferred antibacterial and antifungal target proteins for TQ: D-alanyl-D-alanine synthetase (Ddl) from <i>Thermus thermophilus</i>, transcriptional regulator qacR from <i>Staphylococcus aureus</i>, N-myristoyltransferase from <i>Candida albicans</i>, and NADPH-dependent D-xylose reductase from <i>Candida tenuis.</i> In contrast, the nitroreductase family protein from <i>Bacillus cereus</i> and spore coat polysaccharide biosynthesis protein from <i>Bacillus subtilis</i> and UDP-N-acetylglucosamine pyrophosphorylase from <i>Aspergillus fumigatus</i> are the least preferred antibacterial and antifungal target proteins for TQ, respectively. Molecular dynamics (MD) simulations revealed that TQ could bind to all four target proteins, with Ddl and NADPH-dependent D-xylose reductase being the most efficient. Our findings corroborate TQ’s high antimicrobial potential, suggesting it may be a promising drug candidate for multi-drug resistant (MDR) pathogens, notably Gram-positive bacteria and <i>Candida albicans.</i> |
| first_indexed | 2024-03-10T03:01:47Z |
| format | Article |
| id | doaj.art-7262448511bf48c0aa966512560d5a32 |
| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-10T03:01:47Z |
| publishDate | 2022-01-01 |
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| series | Antibiotics |
| spelling | doaj.art-7262448511bf48c0aa966512560d5a322023-11-23T12:44:41ZengMDPI AGAntibiotics2079-63822022-01-011117910.3390/antibiotics11010079In Vitro and In Silico Approaches for the Evaluation of Antimicrobial Activity, Time-Kill Kinetics, and Anti-Biofilm Potential of Thymoquinone (2-Methyl-5-propan-2-ylcyclohexa-2,5-diene-1,4-dione) against Selected Human PathogensKamal A. Qureshi0Mahrukh Imtiaz1Adil Parvez2Pankaj K. Rai3Mariusz Jaremko4Abdul-Hamid Emwas5Avinash D. Bholay6Muhammad Qaiser Fatmi7Department of Pharmaceutics, Unaizah College of Pharmacy, Qassim University, Unaizah 51911, Saudi ArabiaDepartment of Biosciences, COMSATS University Islamabad, Islamabad 45600, PakistanDepartment of Biotechnology, School of Chemical and Life Sciences, Jamia Hamdard University, New Delhi 110062, IndiaDepartment of Biotechnology, Faculty of Biosciences, Invertis University, Bareilly 243123, IndiaSmart-Health Initiative (SHI) and Red Sea Research Center (RSRC), Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955, Saudi ArabiaCore Labs, King Abdullah University of Science and Technology (KAUST), Thuwal 23955, Saudi ArabiaDepartment of Microbiology, KTHM College, Savitribai Phule Pune University (SPPU), Nashik 422002, IndiaDepartment of Biosciences, COMSATS University Islamabad, Islamabad 45600, PakistanThymoquinone (2-methyl-5-propan-2-ylcyclohexa-2,5-diene-1,4-dione; TQ), a principal bioactive phytoconstituent of <i>Nigella sativa</i> essential oil, has been reported to have high antimicrobial potential. Thus, the current study evaluated TQ’s antimicrobial potential against a range of selected human pathogens using in vitro assays, including time-kill kinetics and anti-biofilm activity. In silico molecular docking of TQ against several antimicrobial target proteins and a detailed intermolecular interaction analysis was performed, including binding energies and docking feasibility. Of the tested bacteria and fungi, <i>S. epidermidis</i> ATCC 12228 and <i>Candida albicans</i> ATCC 10231 were the most susceptible to TQ, with 50.3 ± 0.3 mm and 21.1 ± 0.1 mm zones of inhibition, respectively. Minimum inhibitory concentration (MIC) values of TQ are in the range of 12.5–50 µg/mL, while minimum biocidal concentration (MBC) values are in the range of 25–100 µg/mL against the tested organisms. Time-kill kinetics of TQ revealed that the killing time for the tested bacteria is in the range of 1–6 h with the MBC of TQ. Anti-biofilm activity results demonstrate that the minimum biofilm inhibitory concentration (MBIC) values of TQ are in the range of 25–50 µg/mL, while the minimum biofilm eradication concentration (MBEC) values are in the range of 25–100 µg/mL, for the tested bacteria. In silico molecular docking studies revealed four preferred antibacterial and antifungal target proteins for TQ: D-alanyl-D-alanine synthetase (Ddl) from <i>Thermus thermophilus</i>, transcriptional regulator qacR from <i>Staphylococcus aureus</i>, N-myristoyltransferase from <i>Candida albicans</i>, and NADPH-dependent D-xylose reductase from <i>Candida tenuis.</i> In contrast, the nitroreductase family protein from <i>Bacillus cereus</i> and spore coat polysaccharide biosynthesis protein from <i>Bacillus subtilis</i> and UDP-N-acetylglucosamine pyrophosphorylase from <i>Aspergillus fumigatus</i> are the least preferred antibacterial and antifungal target proteins for TQ, respectively. Molecular dynamics (MD) simulations revealed that TQ could bind to all four target proteins, with Ddl and NADPH-dependent D-xylose reductase being the most efficient. Our findings corroborate TQ’s high antimicrobial potential, suggesting it may be a promising drug candidate for multi-drug resistant (MDR) pathogens, notably Gram-positive bacteria and <i>Candida albicans.</i>https://www.mdpi.com/2079-6382/11/1/79antimicrobial activityanti-biofilm activitymolecular dockingmolecular dynamics simulationstime-kill kineticsthymoquinone |
| spellingShingle | Kamal A. Qureshi Mahrukh Imtiaz Adil Parvez Pankaj K. Rai Mariusz Jaremko Abdul-Hamid Emwas Avinash D. Bholay Muhammad Qaiser Fatmi In Vitro and In Silico Approaches for the Evaluation of Antimicrobial Activity, Time-Kill Kinetics, and Anti-Biofilm Potential of Thymoquinone (2-Methyl-5-propan-2-ylcyclohexa-2,5-diene-1,4-dione) against Selected Human Pathogens Antibiotics antimicrobial activity anti-biofilm activity molecular docking molecular dynamics simulations time-kill kinetics thymoquinone |
| title | In Vitro and In Silico Approaches for the Evaluation of Antimicrobial Activity, Time-Kill Kinetics, and Anti-Biofilm Potential of Thymoquinone (2-Methyl-5-propan-2-ylcyclohexa-2,5-diene-1,4-dione) against Selected Human Pathogens |
| title_full | In Vitro and In Silico Approaches for the Evaluation of Antimicrobial Activity, Time-Kill Kinetics, and Anti-Biofilm Potential of Thymoquinone (2-Methyl-5-propan-2-ylcyclohexa-2,5-diene-1,4-dione) against Selected Human Pathogens |
| title_fullStr | In Vitro and In Silico Approaches for the Evaluation of Antimicrobial Activity, Time-Kill Kinetics, and Anti-Biofilm Potential of Thymoquinone (2-Methyl-5-propan-2-ylcyclohexa-2,5-diene-1,4-dione) against Selected Human Pathogens |
| title_full_unstemmed | In Vitro and In Silico Approaches for the Evaluation of Antimicrobial Activity, Time-Kill Kinetics, and Anti-Biofilm Potential of Thymoquinone (2-Methyl-5-propan-2-ylcyclohexa-2,5-diene-1,4-dione) against Selected Human Pathogens |
| title_short | In Vitro and In Silico Approaches for the Evaluation of Antimicrobial Activity, Time-Kill Kinetics, and Anti-Biofilm Potential of Thymoquinone (2-Methyl-5-propan-2-ylcyclohexa-2,5-diene-1,4-dione) against Selected Human Pathogens |
| title_sort | in vitro and in silico approaches for the evaluation of antimicrobial activity time kill kinetics and anti biofilm potential of thymoquinone 2 methyl 5 propan 2 ylcyclohexa 2 5 diene 1 4 dione against selected human pathogens |
| topic | antimicrobial activity anti-biofilm activity molecular docking molecular dynamics simulations time-kill kinetics thymoquinone |
| url | https://www.mdpi.com/2079-6382/11/1/79 |
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