Synthetic Pathways to Non-Psychotropic Phytocannabinoids as Promising Molecules to Develop Novel Antibiotics: A Review
Due to the rapid emergence of multi drug resistant (MDR) pathogens against which current antibiotics are no longer functioning, severe infections are becoming practically untreatable. Consequently, the discovery of new classes of effective antimicrobial agents with novel mechanism of action is becom...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-07-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/7/1889 |
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| author | Silvana Alfei Gian Carlo Schito Anna Maria Schito |
| author_facet | Silvana Alfei Gian Carlo Schito Anna Maria Schito |
| author_sort | Silvana Alfei |
| collection | DOAJ |
| description | Due to the rapid emergence of multi drug resistant (MDR) pathogens against which current antibiotics are no longer functioning, severe infections are becoming practically untreatable. Consequently, the discovery of new classes of effective antimicrobial agents with novel mechanism of action is becoming increasingly urgent. The bioactivity of <i>Cannabis sativa</i>, an herbaceous plant used for millennia for medicinal and recreational purposes, is mainly due to its content in phytocannabinoids (PCs). Among the 180 PCs detected, cannabidiol (CBD), Δ<sup>8</sup> and Δ<sup>9</sup>-tetrahydrocannabinols (Δ<sup>8</sup>-THC and Δ<sup>9</sup>-THC), cannabichromene (CBC), cannabigerol (CBG), cannabinol (CBN) and some of their acidic precursors have demonstrated from moderate to potent antibacterial effects against Gram-positive bacteria (MICs 0.5–8 µg/mL), including methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), epidemic MRSA (EMRSA), as well as fluoroquinolone and tetracycline-resistant strains. Particularly, the non-psychotropic CBG was also capable to inhibit MRSA biofilm formation, to eradicate even mature biofilms, and to rapidly eliminate MRSA persiter cells. In this scenario, CBG, as well as other minor non-psychotropic PCs, such as CBD, and CBC could represent promising compounds for developing novel antibiotics with high therapeutic potential. Anyway, further studies are necessary, needing abundant quantities of such PCs, scarcely provided naturally by <i>Cannabis</i> plants. Here, after an extensive overture on cannabinoids including their reported antimicrobial effects, aiming at easing the synthetic production of the necessary amounts of CBG, CBC and CBD for further studies, we have, for the first time, systematically reviewed the synthetic pathways utilized for their synthesis, reporting both reaction schemes and experimental details. |
| first_indexed | 2024-03-11T00:44:06Z |
| format | Article |
| id | doaj.art-97e2d3c6035b40d98d1d3928583b8479 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T00:44:06Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-97e2d3c6035b40d98d1d3928583b84792023-11-18T20:55:15ZengMDPI AGPharmaceutics1999-49232023-07-01157188910.3390/pharmaceutics15071889Synthetic Pathways to Non-Psychotropic Phytocannabinoids as Promising Molecules to Develop Novel Antibiotics: A ReviewSilvana Alfei0Gian Carlo Schito1Anna Maria Schito2Department of Pharmacy (DIFAR), University of Genoa, Viale Cembrano, 4, 16148 Genoa, ItalyDepartment of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Viale Benedetto XV, 6, 16132 Genova, ItalyDepartment of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Viale Benedetto XV, 6, 16132 Genova, ItalyDue to the rapid emergence of multi drug resistant (MDR) pathogens against which current antibiotics are no longer functioning, severe infections are becoming practically untreatable. Consequently, the discovery of new classes of effective antimicrobial agents with novel mechanism of action is becoming increasingly urgent. The bioactivity of <i>Cannabis sativa</i>, an herbaceous plant used for millennia for medicinal and recreational purposes, is mainly due to its content in phytocannabinoids (PCs). Among the 180 PCs detected, cannabidiol (CBD), Δ<sup>8</sup> and Δ<sup>9</sup>-tetrahydrocannabinols (Δ<sup>8</sup>-THC and Δ<sup>9</sup>-THC), cannabichromene (CBC), cannabigerol (CBG), cannabinol (CBN) and some of their acidic precursors have demonstrated from moderate to potent antibacterial effects against Gram-positive bacteria (MICs 0.5–8 µg/mL), including methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), epidemic MRSA (EMRSA), as well as fluoroquinolone and tetracycline-resistant strains. Particularly, the non-psychotropic CBG was also capable to inhibit MRSA biofilm formation, to eradicate even mature biofilms, and to rapidly eliminate MRSA persiter cells. In this scenario, CBG, as well as other minor non-psychotropic PCs, such as CBD, and CBC could represent promising compounds for developing novel antibiotics with high therapeutic potential. Anyway, further studies are necessary, needing abundant quantities of such PCs, scarcely provided naturally by <i>Cannabis</i> plants. Here, after an extensive overture on cannabinoids including their reported antimicrobial effects, aiming at easing the synthetic production of the necessary amounts of CBG, CBC and CBD for further studies, we have, for the first time, systematically reviewed the synthetic pathways utilized for their synthesis, reporting both reaction schemes and experimental details.https://www.mdpi.com/1999-4923/15/7/1889bacterial resistancemethicillin-resistant <i>S. aureus</i> (MRSA)multi drug resistant (MDR) bacteria<i>Cannabis sativa</i>phytocannabinoids (PCs)endocannabinois (ECs) |
| spellingShingle | Silvana Alfei Gian Carlo Schito Anna Maria Schito Synthetic Pathways to Non-Psychotropic Phytocannabinoids as Promising Molecules to Develop Novel Antibiotics: A Review Pharmaceutics bacterial resistance methicillin-resistant <i>S. aureus</i> (MRSA) multi drug resistant (MDR) bacteria <i>Cannabis sativa</i> phytocannabinoids (PCs) endocannabinois (ECs) |
| title | Synthetic Pathways to Non-Psychotropic Phytocannabinoids as Promising Molecules to Develop Novel Antibiotics: A Review |
| title_full | Synthetic Pathways to Non-Psychotropic Phytocannabinoids as Promising Molecules to Develop Novel Antibiotics: A Review |
| title_fullStr | Synthetic Pathways to Non-Psychotropic Phytocannabinoids as Promising Molecules to Develop Novel Antibiotics: A Review |
| title_full_unstemmed | Synthetic Pathways to Non-Psychotropic Phytocannabinoids as Promising Molecules to Develop Novel Antibiotics: A Review |
| title_short | Synthetic Pathways to Non-Psychotropic Phytocannabinoids as Promising Molecules to Develop Novel Antibiotics: A Review |
| title_sort | synthetic pathways to non psychotropic phytocannabinoids as promising molecules to develop novel antibiotics a review |
| topic | bacterial resistance methicillin-resistant <i>S. aureus</i> (MRSA) multi drug resistant (MDR) bacteria <i>Cannabis sativa</i> phytocannabinoids (PCs) endocannabinois (ECs) |
| url | https://www.mdpi.com/1999-4923/15/7/1889 |
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