Virtual Screening, Synthesis and Biological Evaluation of <i>Streptococcus mutans</i> Mediated Biofilm Inhibitors
Dental caries, a global oral health concern, is a biofilm-mediated disease. Streptococcus mutans, the most prevalent oral microbiota, produces extracellular enzymes, including glycosyltransferases responsible for sucrose polymerization. In bacterial communities, the biofilm matrix confers resistance...
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MDPI AG
2022-02-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/4/1455 |
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| author | Lubna Atta Ruqaiya Khalil Khalid Mohammed Khan Moatter Zehra Faiza Saleem Mohammad Nur-e-Alam Zaheer Ul-Haq |
| author_facet | Lubna Atta Ruqaiya Khalil Khalid Mohammed Khan Moatter Zehra Faiza Saleem Mohammad Nur-e-Alam Zaheer Ul-Haq |
| author_sort | Lubna Atta |
| collection | DOAJ |
| description | Dental caries, a global oral health concern, is a biofilm-mediated disease. Streptococcus mutans, the most prevalent oral microbiota, produces extracellular enzymes, including glycosyltransferases responsible for sucrose polymerization. In bacterial communities, the biofilm matrix confers resistance to host immune responses and antibiotics. Thus, in cases of chronic dental caries, inhibiting bacterial biofilm assembly should prevent demineralization of tooth enamel, thereby preventing tooth decay. A high throughput screening was performed in the present study to identify small molecule inhibitors of <i>S. mutans</i> glycosyltransferases. Multiple pharmacophore models were developed, validated with multiple datasets, and used for virtual screening against large chemical databases. Over 3000 drug-like hits were obtained that were analyzed to explore their binding mode. Finally, six compounds that showed good binding affinities were further analyzed for ADME (absorption, distribution, metabolism, and excretion) properties. The obtained in silico hits were evaluated for in vitro biofilm formation. The compounds displayed excellent antibiofilm activities with minimum inhibitory concentration (MIC) values of 15.26–250 µg/mL. |
| first_indexed | 2024-03-09T21:20:01Z |
| format | Article |
| id | doaj.art-a09f696aea7d46bcbee359dc3a4b369d |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T21:20:01Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-a09f696aea7d46bcbee359dc3a4b369d2023-11-23T21:24:15ZengMDPI AGMolecules1420-30492022-02-01274145510.3390/molecules27041455Virtual Screening, Synthesis and Biological Evaluation of <i>Streptococcus mutans</i> Mediated Biofilm InhibitorsLubna Atta0Ruqaiya Khalil1Khalid Mohammed Khan2Moatter Zehra3Faiza Saleem4Mohammad Nur-e-Alam5Zaheer Ul-Haq6H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, PakistanDr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, PakistanH. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, PakistanDr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, PakistanH. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, PakistanDepartment of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi ArabiaH. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, PakistanDental caries, a global oral health concern, is a biofilm-mediated disease. Streptococcus mutans, the most prevalent oral microbiota, produces extracellular enzymes, including glycosyltransferases responsible for sucrose polymerization. In bacterial communities, the biofilm matrix confers resistance to host immune responses and antibiotics. Thus, in cases of chronic dental caries, inhibiting bacterial biofilm assembly should prevent demineralization of tooth enamel, thereby preventing tooth decay. A high throughput screening was performed in the present study to identify small molecule inhibitors of <i>S. mutans</i> glycosyltransferases. Multiple pharmacophore models were developed, validated with multiple datasets, and used for virtual screening against large chemical databases. Over 3000 drug-like hits were obtained that were analyzed to explore their binding mode. Finally, six compounds that showed good binding affinities were further analyzed for ADME (absorption, distribution, metabolism, and excretion) properties. The obtained in silico hits were evaluated for in vitro biofilm formation. The compounds displayed excellent antibiofilm activities with minimum inhibitory concentration (MIC) values of 15.26–250 µg/mL.https://www.mdpi.com/1420-3049/27/4/1455dental cariesbiofilmglucosyltransferasesvirtual screeningantibiofilmantimicrobial ADMET profiling |
| spellingShingle | Lubna Atta Ruqaiya Khalil Khalid Mohammed Khan Moatter Zehra Faiza Saleem Mohammad Nur-e-Alam Zaheer Ul-Haq Virtual Screening, Synthesis and Biological Evaluation of <i>Streptococcus mutans</i> Mediated Biofilm Inhibitors Molecules dental caries biofilm glucosyltransferases virtual screening antibiofilm antimicrobial ADMET profiling |
| title | Virtual Screening, Synthesis and Biological Evaluation of <i>Streptococcus mutans</i> Mediated Biofilm Inhibitors |
| title_full | Virtual Screening, Synthesis and Biological Evaluation of <i>Streptococcus mutans</i> Mediated Biofilm Inhibitors |
| title_fullStr | Virtual Screening, Synthesis and Biological Evaluation of <i>Streptococcus mutans</i> Mediated Biofilm Inhibitors |
| title_full_unstemmed | Virtual Screening, Synthesis and Biological Evaluation of <i>Streptococcus mutans</i> Mediated Biofilm Inhibitors |
| title_short | Virtual Screening, Synthesis and Biological Evaluation of <i>Streptococcus mutans</i> Mediated Biofilm Inhibitors |
| title_sort | virtual screening synthesis and biological evaluation of i streptococcus mutans i mediated biofilm inhibitors |
| topic | dental caries biofilm glucosyltransferases virtual screening antibiofilm antimicrobial ADMET profiling |
| url | https://www.mdpi.com/1420-3049/27/4/1455 |
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