<i>Euphorbia</i> Diterpenes: An Update of Isolation, Structure, Pharmacological Activities and Structure–Activity Relationship
<i>Euphorbia</i> species have a rich history of ethnomedicinal use and ethnopharmacological applications in drug discovery. This is due to the presence of a wide range of diterpenes exhibiting great structural diversity and pharmacological activities. As a result, <i>Euphorbia</...
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MDPI AG
2021-08-01
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| Schriftenreihe: | Molecules |
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| Online Zugang: | https://www.mdpi.com/1420-3049/26/16/5055 |
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| author | Douglas Kemboi Xavier Siwe-Noundou Rui W. M. Krause Moses K. Langat Vuyelwa Jacqueline Tembu |
| author_facet | Douglas Kemboi Xavier Siwe-Noundou Rui W. M. Krause Moses K. Langat Vuyelwa Jacqueline Tembu |
| author_sort | Douglas Kemboi |
| collection | DOAJ |
| description | <i>Euphorbia</i> species have a rich history of ethnomedicinal use and ethnopharmacological applications in drug discovery. This is due to the presence of a wide range of diterpenes exhibiting great structural diversity and pharmacological activities. As a result, <i>Euphorbia</i> diterpenes have remained the focus of drug discovery investigations from natural products. The current review documents over 350 diterpenes, isolated from <i>Euphorbia</i> species, their structures, classification, biosynthetic pathways, and their structure–activity relationships for the period covering 2013–2020. Among the isolated diterpenes, over 20 skeletal structures were identified. Lathyrane, jatrophane, ingenane, ingenol, and ingol were identified as the major diterpenes in most <i>Euphorbia</i> species. Most of the isolated diterpenes were evaluated for their cytotoxicity activities, multidrug resistance abilities, and inhibitory activities in vitro, and reported good activities with significant half-inhibitory concentration (IC<sub>50</sub>) values ranging from 10–50 µM. The lathyranes, isopimaranes, and jatrophanes diterpenes were further found to show potent inhibition of P-glycoprotein, which is known to confer drug resistance abilities in cells leading to decreased cytotoxic effects. Structure–activity relationship (SAR) studies revealed the significance of a free hydroxyl group at position C-3 in enhancing the anticancer and anti-inflammatory activities and the negative effect it has in position C-2. Esterification of this functionality, in selected diterpenes, was found to enhance these activities. Thus, <i>Euphorbia</i> diterpenes offer a valuable source of lead compounds that could be investigated further as potential candidates for drug discovery. |
| first_indexed | 2024-03-10T08:31:57Z |
| format | Article |
| id | doaj.art-2997c4c8e9e04431a2c09ae986833063 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T08:31:57Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-2997c4c8e9e04431a2c09ae9868330632023-11-22T08:55:57ZengMDPI AGMolecules1420-30492021-08-012616505510.3390/molecules26165055<i>Euphorbia</i> Diterpenes: An Update of Isolation, Structure, Pharmacological Activities and Structure–Activity RelationshipDouglas Kemboi0Xavier Siwe-Noundou1Rui W. M. Krause2Moses K. Langat3Vuyelwa Jacqueline Tembu4Department of Chemistry, Faculty of Science, Tshwane University of Technology, Pretoria 0001, South AfricaDepartment of Chemistry, Rhodes University, Makhanda 6140, South AfricaDepartment of Chemistry, Rhodes University, Makhanda 6140, South AfricaJodrell Laboratory, Department of Unlocking Properties, Royal Botanic Gardens Kew, Richmond TW9 3DS, UKDepartment of Chemistry, Faculty of Science, Tshwane University of Technology, Pretoria 0001, South Africa<i>Euphorbia</i> species have a rich history of ethnomedicinal use and ethnopharmacological applications in drug discovery. This is due to the presence of a wide range of diterpenes exhibiting great structural diversity and pharmacological activities. As a result, <i>Euphorbia</i> diterpenes have remained the focus of drug discovery investigations from natural products. The current review documents over 350 diterpenes, isolated from <i>Euphorbia</i> species, their structures, classification, biosynthetic pathways, and their structure–activity relationships for the period covering 2013–2020. Among the isolated diterpenes, over 20 skeletal structures were identified. Lathyrane, jatrophane, ingenane, ingenol, and ingol were identified as the major diterpenes in most <i>Euphorbia</i> species. Most of the isolated diterpenes were evaluated for their cytotoxicity activities, multidrug resistance abilities, and inhibitory activities in vitro, and reported good activities with significant half-inhibitory concentration (IC<sub>50</sub>) values ranging from 10–50 µM. The lathyranes, isopimaranes, and jatrophanes diterpenes were further found to show potent inhibition of P-glycoprotein, which is known to confer drug resistance abilities in cells leading to decreased cytotoxic effects. Structure–activity relationship (SAR) studies revealed the significance of a free hydroxyl group at position C-3 in enhancing the anticancer and anti-inflammatory activities and the negative effect it has in position C-2. Esterification of this functionality, in selected diterpenes, was found to enhance these activities. Thus, <i>Euphorbia</i> diterpenes offer a valuable source of lead compounds that could be investigated further as potential candidates for drug discovery.https://www.mdpi.com/1420-3049/26/16/5055<i>Euphorbia</i>diterpenespharmacological activitystructure–activity relationship |
| spellingShingle | Douglas Kemboi Xavier Siwe-Noundou Rui W. M. Krause Moses K. Langat Vuyelwa Jacqueline Tembu <i>Euphorbia</i> Diterpenes: An Update of Isolation, Structure, Pharmacological Activities and Structure–Activity Relationship Molecules <i>Euphorbia</i> diterpenes pharmacological activity structure–activity relationship |
| title | <i>Euphorbia</i> Diterpenes: An Update of Isolation, Structure, Pharmacological Activities and Structure–Activity Relationship |
| title_full | <i>Euphorbia</i> Diterpenes: An Update of Isolation, Structure, Pharmacological Activities and Structure–Activity Relationship |
| title_fullStr | <i>Euphorbia</i> Diterpenes: An Update of Isolation, Structure, Pharmacological Activities and Structure–Activity Relationship |
| title_full_unstemmed | <i>Euphorbia</i> Diterpenes: An Update of Isolation, Structure, Pharmacological Activities and Structure–Activity Relationship |
| title_short | <i>Euphorbia</i> Diterpenes: An Update of Isolation, Structure, Pharmacological Activities and Structure–Activity Relationship |
| title_sort | i euphorbia i diterpenes an update of isolation structure pharmacological activities and structure activity relationship |
| topic | <i>Euphorbia</i> diterpenes pharmacological activity structure–activity relationship |
| url | https://www.mdpi.com/1420-3049/26/16/5055 |
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