Synthesis and Biological Evaluation of Carvacrol-Based Derivatives as Dual Inhibitors of <i>H. pylori</i> Strains and AGS Cell Proliferation
This study reports on the synthesis, structural assessment, microbiological screening against several strains of <i>H. pylori</i> and antiproliferative activity against human gastric adenocarcinoma (AGS) cells of a large series of carvacrol-based compounds. Structural analyses consisted...
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MDPI AG
2020-11-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/13/11/405 |
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| author | Francesca Sisto Simone Carradori Paolo Guglielmi Carmen Beatrice Traversi Mattia Spano Anatoly P. Sobolev Daniela Secci Maria Carmela Di Marcantonio Entela Haloci Rossella Grande Gabriella Mincione |
| author_facet | Francesca Sisto Simone Carradori Paolo Guglielmi Carmen Beatrice Traversi Mattia Spano Anatoly P. Sobolev Daniela Secci Maria Carmela Di Marcantonio Entela Haloci Rossella Grande Gabriella Mincione |
| author_sort | Francesca Sisto |
| collection | DOAJ |
| description | This study reports on the synthesis, structural assessment, microbiological screening against several strains of <i>H. pylori</i> and antiproliferative activity against human gastric adenocarcinoma (AGS) cells of a large series of carvacrol-based compounds. Structural analyses consisted of elemental analysis, <sup>1</sup>H/<sup>13</sup>C/<sup>19</sup>F NMR spectra and crystallographic studies. The structure-activity relationships evidenced that among ether derivatives the substitution with specific electron-withdrawing groups (CF<sub>3</sub> and NO<sub>2</sub>) especially in the para position of the benzyl ring led to an improvement of the antimicrobial activity, whereas electron-donating groups on the benzyl ring and ethereal alkyl chains were not tolerated with respect to the parent compound (MIC/MBC = 64/64 µg/mL). Ester derivatives (coumarin-carvacrol hybrids) displayed a slight enhancement of the inhibitory activity up to MIC values of 8–16 µg/mL. The most interesting compounds exhibiting the lowest MIC/MBC activity against <i>H. pylori</i> (among others, compounds <b>16</b> and <b>39</b> endowed with MIC/MBC values ranging between 2/2 to 32/32 µg/mL against all the evaluated strains) were also assayed for their ability to reduce AGS cell growth with respect to 5-Fluorouracil. Some derivatives can be regarded as new lead compounds able to reduce <i>H. pylori</i> growth and to counteract the proliferation of AGS cells, both contributing to the occurrence of gastric cancer. |
| first_indexed | 2024-03-10T14:43:47Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T14:43:47Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-58e004b624244ea18d0303b32d3fb6482023-11-20T21:33:15ZengMDPI AGPharmaceuticals1424-82472020-11-01131140510.3390/ph13110405Synthesis and Biological Evaluation of Carvacrol-Based Derivatives as Dual Inhibitors of <i>H. pylori</i> Strains and AGS Cell ProliferationFrancesca Sisto0Simone Carradori1Paolo Guglielmi2Carmen Beatrice Traversi3Mattia Spano4Anatoly P. Sobolev5Daniela Secci6Maria Carmela Di Marcantonio7Entela Haloci8Rossella Grande9Gabriella 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 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, ItalyInstitute for Biological Systems, “Annalaura Segre” Magnetic Resonance Laboratory, CNR, 00015 Monterotondo (Rome), ItalyDepartment of Chemistry and Technology of Drugs, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, ItalyDepartment of Medical, Oral, and Biotechnological Sciences, “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, ItalyDepartment of Pharmacy, University of Medicine, Tirana, Rr. Dibres 369, 1001 Tirana, AlbaniaDepartment of Pharmacy, “G. d’Annunzio” University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, ItalyDepartment of Medical, Oral, and Biotechnological Sciences, “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, ItalyThis study reports on the synthesis, structural assessment, microbiological screening against several strains of <i>H. pylori</i> and antiproliferative activity against human gastric adenocarcinoma (AGS) cells of a large series of carvacrol-based compounds. Structural analyses consisted of elemental analysis, <sup>1</sup>H/<sup>13</sup>C/<sup>19</sup>F NMR spectra and crystallographic studies. The structure-activity relationships evidenced that among ether derivatives the substitution with specific electron-withdrawing groups (CF<sub>3</sub> and NO<sub>2</sub>) especially in the para position of the benzyl ring led to an improvement of the antimicrobial activity, whereas electron-donating groups on the benzyl ring and ethereal alkyl chains were not tolerated with respect to the parent compound (MIC/MBC = 64/64 µg/mL). Ester derivatives (coumarin-carvacrol hybrids) displayed a slight enhancement of the inhibitory activity up to MIC values of 8–16 µg/mL. The most interesting compounds exhibiting the lowest MIC/MBC activity against <i>H. pylori</i> (among others, compounds <b>16</b> and <b>39</b> endowed with MIC/MBC values ranging between 2/2 to 32/32 µg/mL against all the evaluated strains) were also assayed for their ability to reduce AGS cell growth with respect to 5-Fluorouracil. Some derivatives can be regarded as new lead compounds able to reduce <i>H. pylori</i> growth and to counteract the proliferation of AGS cells, both contributing to the occurrence of gastric cancer.https://www.mdpi.com/1424-8247/13/11/405carvacrol<i>Helicobacter pylori</i>AGS cellssemi-synthesisdrug resistancedual agent |
| spellingShingle | Francesca Sisto Simone Carradori Paolo Guglielmi Carmen Beatrice Traversi Mattia Spano Anatoly P. Sobolev Daniela Secci Maria Carmela Di Marcantonio Entela Haloci Rossella Grande Gabriella Mincione Synthesis and Biological Evaluation of Carvacrol-Based Derivatives as Dual Inhibitors of <i>H. pylori</i> Strains and AGS Cell Proliferation Pharmaceuticals carvacrol <i>Helicobacter pylori</i> AGS cells semi-synthesis drug resistance dual agent |
| title | Synthesis and Biological Evaluation of Carvacrol-Based Derivatives as Dual Inhibitors of <i>H. pylori</i> Strains and AGS Cell Proliferation |
| title_full | Synthesis and Biological Evaluation of Carvacrol-Based Derivatives as Dual Inhibitors of <i>H. pylori</i> Strains and AGS Cell Proliferation |
| title_fullStr | Synthesis and Biological Evaluation of Carvacrol-Based Derivatives as Dual Inhibitors of <i>H. pylori</i> Strains and AGS Cell Proliferation |
| title_full_unstemmed | Synthesis and Biological Evaluation of Carvacrol-Based Derivatives as Dual Inhibitors of <i>H. pylori</i> Strains and AGS Cell Proliferation |
| title_short | Synthesis and Biological Evaluation of Carvacrol-Based Derivatives as Dual Inhibitors of <i>H. pylori</i> Strains and AGS Cell Proliferation |
| title_sort | synthesis and biological evaluation of carvacrol based derivatives as dual inhibitors of i h pylori i strains and ags cell proliferation |
| topic | carvacrol <i>Helicobacter pylori</i> AGS cells semi-synthesis drug resistance dual agent |
| url | https://www.mdpi.com/1424-8247/13/11/405 |
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