Efficient Synthesis for Altering Side Chain Length on Cannabinoid Molecules and Their Effects in Chemotherapy and Chemotherapeutic Induced Neuropathic Pain
(1) Background: Recently, a number of side chain length variants for tetrahydrocannabinol and cannabidiol have been identified in cannabis; however, the precursor to these molecules would be based upon cannabigerol (CBG). Because CBG, and its side chain variants, are rapidly converted to other canna...
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| Format: | Article |
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MDPI AG
2022-12-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/12/12/1869 |
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| author | Wesley M. Raup-Konsavage Diana E. Sepulveda Daniel P. Morris Shantu Amin Kent E. Vrana Nicholas M. Graziane Dhimant Desai |
| author_facet | Wesley M. Raup-Konsavage Diana E. Sepulveda Daniel P. Morris Shantu Amin Kent E. Vrana Nicholas M. Graziane Dhimant Desai |
| author_sort | Wesley M. Raup-Konsavage |
| collection | DOAJ |
| description | (1) Background: Recently, a number of side chain length variants for tetrahydrocannabinol and cannabidiol have been identified in cannabis; however, the precursor to these molecules would be based upon cannabigerol (CBG). Because CBG, and its side chain variants, are rapidly converted to other cannabinoids in the plant, there are typically only small amounts in plant extracts, thus prohibiting investigations related to CBG and CBG variant therapeutic effects. (2) Methods: To overcome this, we developed an efficient synthesis of corresponding resorcinol fragments using the Wittig reaction which, under acid catalyzed coupling with geraniol, produced the desired side chain variants of CBG. These compounds were then tested in an animal model of chemotherapeutic-induced neuropathic pain and to reduce colorectal cancer cell viability. (3) Results: We found that all side-chain variants were similarly capable of reducing neuropathic pain in mice at a dose of 10 mg/kg. However, the molecules with shorter side chains (i.e., CBGV and CBGB) were better at reducing colorectal cancer cell viability. (4) Conclusions: The novel synthesis method developed here will be of utility for studying other side chain derivatives of minor cannabinoids such as cannabichromene, cannabinol, and cannabielsoin. |
| first_indexed | 2024-03-09T17:16:29Z |
| format | Article |
| id | doaj.art-a89190cda6d64ddfa99cf6a13b430b30 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T17:16:29Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-a89190cda6d64ddfa99cf6a13b430b302023-11-24T13:34:46ZengMDPI AGBiomolecules2218-273X2022-12-011212186910.3390/biom12121869Efficient Synthesis for Altering Side Chain Length on Cannabinoid Molecules and Their Effects in Chemotherapy and Chemotherapeutic Induced Neuropathic PainWesley M. Raup-Konsavage0Diana E. Sepulveda1Daniel P. Morris2Shantu Amin3Kent E. Vrana4Nicholas M. Graziane5Dhimant Desai6Department of Pharmacology, Penn State College of Medicine, Hershey, PA 17033, USADepartment of Pharmacology, Penn State College of Medicine, Hershey, PA 17033, USADepartment of Pharmacology, Penn State College of Medicine, Hershey, PA 17033, USADepartment of Pharmacology, Penn State College of Medicine, Hershey, PA 17033, USADepartment of Pharmacology, Penn State College of Medicine, Hershey, PA 17033, USADepartment of Pharmacology, Penn State College of Medicine, Hershey, PA 17033, USADepartment of Pharmacology, Penn State College of Medicine, Hershey, PA 17033, USA(1) Background: Recently, a number of side chain length variants for tetrahydrocannabinol and cannabidiol have been identified in cannabis; however, the precursor to these molecules would be based upon cannabigerol (CBG). Because CBG, and its side chain variants, are rapidly converted to other cannabinoids in the plant, there are typically only small amounts in plant extracts, thus prohibiting investigations related to CBG and CBG variant therapeutic effects. (2) Methods: To overcome this, we developed an efficient synthesis of corresponding resorcinol fragments using the Wittig reaction which, under acid catalyzed coupling with geraniol, produced the desired side chain variants of CBG. These compounds were then tested in an animal model of chemotherapeutic-induced neuropathic pain and to reduce colorectal cancer cell viability. (3) Results: We found that all side-chain variants were similarly capable of reducing neuropathic pain in mice at a dose of 10 mg/kg. However, the molecules with shorter side chains (i.e., CBGV and CBGB) were better at reducing colorectal cancer cell viability. (4) Conclusions: The novel synthesis method developed here will be of utility for studying other side chain derivatives of minor cannabinoids such as cannabichromene, cannabinol, and cannabielsoin.https://www.mdpi.com/2218-273X/12/12/1869cannabigerolneuropathic paincolorectal cancercannabinoid synthesis |
| spellingShingle | Wesley M. Raup-Konsavage Diana E. Sepulveda Daniel P. Morris Shantu Amin Kent E. Vrana Nicholas M. Graziane Dhimant Desai Efficient Synthesis for Altering Side Chain Length on Cannabinoid Molecules and Their Effects in Chemotherapy and Chemotherapeutic Induced Neuropathic Pain Biomolecules cannabigerol neuropathic pain colorectal cancer cannabinoid synthesis |
| title | Efficient Synthesis for Altering Side Chain Length on Cannabinoid Molecules and Their Effects in Chemotherapy and Chemotherapeutic Induced Neuropathic Pain |
| title_full | Efficient Synthesis for Altering Side Chain Length on Cannabinoid Molecules and Their Effects in Chemotherapy and Chemotherapeutic Induced Neuropathic Pain |
| title_fullStr | Efficient Synthesis for Altering Side Chain Length on Cannabinoid Molecules and Their Effects in Chemotherapy and Chemotherapeutic Induced Neuropathic Pain |
| title_full_unstemmed | Efficient Synthesis for Altering Side Chain Length on Cannabinoid Molecules and Their Effects in Chemotherapy and Chemotherapeutic Induced Neuropathic Pain |
| title_short | Efficient Synthesis for Altering Side Chain Length on Cannabinoid Molecules and Their Effects in Chemotherapy and Chemotherapeutic Induced Neuropathic Pain |
| title_sort | efficient synthesis for altering side chain length on cannabinoid molecules and their effects in chemotherapy and chemotherapeutic induced neuropathic pain |
| topic | cannabigerol neuropathic pain colorectal cancer cannabinoid synthesis |
| url | https://www.mdpi.com/2218-273X/12/12/1869 |
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