Synthesis and Evaluation of Thymol-Based Synthetic Derivatives as Dual-Action Inhibitors against Different Strains of <i>H. pylori</i> and AGS Cell Line
Following a similar approach on carvacrol-based derivatives, we investigated the synthesis and the microbiological screening against eight strains of <i>H. pylori</i>, and the cytotoxic activity against human gastric adenocarcinoma (AGS) cells of a new series of ether compounds based on...
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MDPI AG
2021-03-01
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| Online Access: | https://www.mdpi.com/1420-3049/26/7/1829 |
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| author | Francesca Sisto Simone Carradori Paolo Guglielmi Mattia Spano Daniela Secci Arianna Granese Anatoly P. Sobolev Rossella Grande Cristina Campestre Maria Carmela Di Marcantonio Gabriella Mincione |
| author_facet | Francesca Sisto Simone Carradori Paolo Guglielmi Mattia Spano Daniela Secci Arianna Granese Anatoly P. Sobolev Rossella Grande Cristina Campestre Maria Carmela Di Marcantonio Gabriella Mincione |
| author_sort | Francesca Sisto |
| collection | DOAJ |
| description | Following a similar approach on carvacrol-based derivatives, we investigated the synthesis and the microbiological screening against eight strains of <i>H. pylori</i>, and the cytotoxic activity against human gastric adenocarcinoma (AGS) cells of a new series of ether compounds based on the structure of thymol. Structural analysis comprehended elemental analysis and <sup>1</sup>H/<sup>13</sup>C/<sup>19</sup>F NMR spectra. The analysis of structure–activity relationships within this molecular library of 38 structurally-related compounds reported that some chemical modifications of the OH group of thymol led to broad-spectrum growth inhibition on all isolates. Preferred substitutions were benzyl groups compared to alkyl chains, and the specific presence of functional groups at <i>para</i> position of the benzyl moiety such as 4-CN and 4-Ph endowed the most anti-<i>H. pylori</i> activity toward all the strains with minimum inhibitory concentration (MIC) values up to 4 µg/mL. Poly-substitution on the benzyl ring was not essential. Moreover, several compounds characterized by the lowest minimum inhibitory concentration/minimum bactericidal concentration (MIC/MBC) values against <i>H. pylori</i> were also tested in order to verify a cytotoxic effect against AGS cells with respect to 5-fluorouracil and carvacrol. Three derivatives can be considered as new lead compounds alternative to current therapy to manage <i>H. pylori</i> infection, preventing the occurrence of severe gastric diseases. The present work confirms the possibility to use natural compounds as templates for the medicinal semi-synthesis. |
| first_indexed | 2024-03-10T12:56:50Z |
| format | Article |
| id | doaj.art-23380c81b32a46d3a097f55d21393885 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T12:56:50Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-23380c81b32a46d3a097f55d213938852023-11-21T11:50:53ZengMDPI AGMolecules1420-30492021-03-01267182910.3390/molecules26071829Synthesis and Evaluation of Thymol-Based Synthetic Derivatives as Dual-Action Inhibitors against Different Strains of <i>H. pylori</i> and AGS Cell LineFrancesca Sisto0Simone Carradori1Paolo Guglielmi2Mattia Spano3Daniela Secci4Arianna Granese5Anatoly P. Sobolev6Rossella Grande7Cristina Campestre8Maria Carmela Di Marcantonio9Gabriella Mincione10Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, ItalyDepartment of Pharmacy, “G. d’Annunzio” University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, ItalyDepartment of Chemistry and Technology of Drugs, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, ItalyDepartment of Chemistry and Technology of Drugs, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, ItalyDepartment of Chemistry and Technology of Drugs, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, ItalyDepartment of Chemistry and Technology of Drugs, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, ItalyInstitute for Biological Systems, “Annalaura Segre” Magnetic Resonance Laboratory, CNR, 00015 Rome, ItalyDepartment of Pharmacy, “G. d’Annunzio” University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, ItalyDepartment of Pharmacy, “G. d’Annunzio” University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, ItalyDepartment of Innovative Technologies in Medicine and Dentistry, “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, ItalyDepartment of Innovative Technologies in Medicine and Dentistry, “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, ItalyFollowing a similar approach on carvacrol-based derivatives, we investigated the synthesis and the microbiological screening against eight strains of <i>H. pylori</i>, and the cytotoxic activity against human gastric adenocarcinoma (AGS) cells of a new series of ether compounds based on the structure of thymol. Structural analysis comprehended elemental analysis and <sup>1</sup>H/<sup>13</sup>C/<sup>19</sup>F NMR spectra. The analysis of structure–activity relationships within this molecular library of 38 structurally-related compounds reported that some chemical modifications of the OH group of thymol led to broad-spectrum growth inhibition on all isolates. Preferred substitutions were benzyl groups compared to alkyl chains, and the specific presence of functional groups at <i>para</i> position of the benzyl moiety such as 4-CN and 4-Ph endowed the most anti-<i>H. pylori</i> activity toward all the strains with minimum inhibitory concentration (MIC) values up to 4 µg/mL. Poly-substitution on the benzyl ring was not essential. Moreover, several compounds characterized by the lowest minimum inhibitory concentration/minimum bactericidal concentration (MIC/MBC) values against <i>H. pylori</i> were also tested in order to verify a cytotoxic effect against AGS cells with respect to 5-fluorouracil and carvacrol. Three derivatives can be considered as new lead compounds alternative to current therapy to manage <i>H. pylori</i> infection, preventing the occurrence of severe gastric diseases. The present work confirms the possibility to use natural compounds as templates for the medicinal semi-synthesis.https://www.mdpi.com/1420-3049/26/7/1829thymol<i>Helicobacter pylori</i>AGS cellssemi-synthesisdrug resistancedual-action agents, antimicrobial activity |
| spellingShingle | Francesca Sisto Simone Carradori Paolo Guglielmi Mattia Spano Daniela Secci Arianna Granese Anatoly P. Sobolev Rossella Grande Cristina Campestre Maria Carmela Di Marcantonio Gabriella Mincione Synthesis and Evaluation of Thymol-Based Synthetic Derivatives as Dual-Action Inhibitors against Different Strains of <i>H. pylori</i> and AGS Cell Line Molecules thymol <i>Helicobacter pylori</i> AGS cells semi-synthesis drug resistance dual-action agents, antimicrobial activity |
| title | Synthesis and Evaluation of Thymol-Based Synthetic Derivatives as Dual-Action Inhibitors against Different Strains of <i>H. pylori</i> and AGS Cell Line |
| title_full | Synthesis and Evaluation of Thymol-Based Synthetic Derivatives as Dual-Action Inhibitors against Different Strains of <i>H. pylori</i> and AGS Cell Line |
| title_fullStr | Synthesis and Evaluation of Thymol-Based Synthetic Derivatives as Dual-Action Inhibitors against Different Strains of <i>H. pylori</i> and AGS Cell Line |
| title_full_unstemmed | Synthesis and Evaluation of Thymol-Based Synthetic Derivatives as Dual-Action Inhibitors against Different Strains of <i>H. pylori</i> and AGS Cell Line |
| title_short | Synthesis and Evaluation of Thymol-Based Synthetic Derivatives as Dual-Action Inhibitors against Different Strains of <i>H. pylori</i> and AGS Cell Line |
| title_sort | synthesis and evaluation of thymol based synthetic derivatives as dual action inhibitors against different strains of i h pylori i and ags cell line |
| topic | thymol <i>Helicobacter pylori</i> AGS cells semi-synthesis drug resistance dual-action agents, antimicrobial activity |
| url | https://www.mdpi.com/1420-3049/26/7/1829 |
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