Synthesis and Biological Evaluation of Cassane Diterpene (5α)-Vuacapane-8(14), 9(11)-Diene and of Some Related Compounds
A set of thirteen cassane-type diterpenes was synthesized and an expedient synthetic route was used to evaluate 14-desmethyl analogs of the most active tested cassane. The anti-inflammatory activities of these 13 compounds were evaluated on a lipopolysaccharide (LPS)-activated RAW 264.7 cell line by...
| Main Authors: | , , , , , , , , |
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| Format: | info:eu-repo/semantics/article |
| Language: | English |
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MDPI
2022
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| Online Access: | http://hdl.handle.net/10835/13934 |
| _version_ | 1789406378511564800 |
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| author | Zentar, Houda Jannus, Fatin Medina-O’Donnell, Marta Lupiáñez, José A. Justicia, José Alvarez-Manzaneda Roldán, Ramón Jesús Reyes-Zurita, Fernando J. Alvarez-Manzaneda, Enrique Chahboun, Rachid |
| author_facet | Zentar, Houda Jannus, Fatin Medina-O’Donnell, Marta Lupiáñez, José A. Justicia, José Alvarez-Manzaneda Roldán, Ramón Jesús Reyes-Zurita, Fernando J. Alvarez-Manzaneda, Enrique Chahboun, Rachid |
| author_sort | Zentar, Houda |
| collection | DSpace |
| description | A set of thirteen cassane-type diterpenes was synthesized and an expedient synthetic route was used to evaluate 14-desmethyl analogs of the most active tested cassane. The anti-inflammatory activities of these 13 compounds were evaluated on a lipopolysaccharide (LPS)-activated RAW 264.7 cell line by inhibition of nitric oxide (NO) production, some of them reaching 100% NO inhibition after 72 h of treatment. The greatest anti-inflammatory effect was observed for compounds 16 and 20 with an IC50 NO of 2.98 ± 0.04 μg/mL and 5.71 ± 0.14 μg/mL, respectively. Flow-cytometry analysis was used to determine the cell cycle distribution and showed that the inhibition in NO release was accompanied by a reversion of the differentiation processes. Moreover, the anti-cancer potential of these 13 compounds were evaluated in three tumor cell lines (B16-F10, HT29, and Hep G2). The strongest cytotoxic effect was achieved by salicylaldehyde 20, and pterolobirin G (6), with IC50 values around 3 μg/mL in HT29 cells, with total apoptosis rates 80% at IC80 concentrations, producing a significant cell-cycle arrest in the G0/G1 phase, and a possible activation of the extrinsic apoptotic pathway. Additionally, initial SAR data analysis showed that the methyl group at the C-14 positions of cassane diterpenoids is not always important for their cytotoxic and anti-inflammatory activities. |
| format | info:eu-repo/semantics/article |
| id | oai:repositorio.ual.es:10835-13934 |
| institution | Universidad de Cuenca |
| language | English |
| publishDate | 2022 |
| publisher | MDPI |
| record_format | dspace |
| spelling | oai:repositorio.ual.es:10835-139342023-04-12T19:47:07Z Synthesis and Biological Evaluation of Cassane Diterpene (5α)-Vuacapane-8(14), 9(11)-Diene and of Some Related Compounds Zentar, Houda Jannus, Fatin Medina-O’Donnell, Marta Lupiáñez, José A. Justicia, José Alvarez-Manzaneda Roldán, Ramón Jesús Reyes-Zurita, Fernando J. Alvarez-Manzaneda, Enrique Chahboun, Rachid natural products semisynthesis cassane diterpenoids anti-inflammatory activity anti-cancer activity A set of thirteen cassane-type diterpenes was synthesized and an expedient synthetic route was used to evaluate 14-desmethyl analogs of the most active tested cassane. The anti-inflammatory activities of these 13 compounds were evaluated on a lipopolysaccharide (LPS)-activated RAW 264.7 cell line by inhibition of nitric oxide (NO) production, some of them reaching 100% NO inhibition after 72 h of treatment. The greatest anti-inflammatory effect was observed for compounds 16 and 20 with an IC50 NO of 2.98 ± 0.04 μg/mL and 5.71 ± 0.14 μg/mL, respectively. Flow-cytometry analysis was used to determine the cell cycle distribution and showed that the inhibition in NO release was accompanied by a reversion of the differentiation processes. Moreover, the anti-cancer potential of these 13 compounds were evaluated in three tumor cell lines (B16-F10, HT29, and Hep G2). The strongest cytotoxic effect was achieved by salicylaldehyde 20, and pterolobirin G (6), with IC50 values around 3 μg/mL in HT29 cells, with total apoptosis rates 80% at IC80 concentrations, producing a significant cell-cycle arrest in the G0/G1 phase, and a possible activation of the extrinsic apoptotic pathway. Additionally, initial SAR data analysis showed that the methyl group at the C-14 positions of cassane diterpenoids is not always important for their cytotoxic and anti-inflammatory activities. 2022-09-07T16:38:13Z 2022-09-07T16:38:13Z 2022-09-04 info:eu-repo/semantics/article 1420-3049 http://hdl.handle.net/10835/13934 10.3390/molecules27175705 en https://www.mdpi.com/1420-3049/27/17/5705 Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess MDPI |
| spellingShingle | natural products semisynthesis cassane diterpenoids anti-inflammatory activity anti-cancer activity Zentar, Houda Jannus, Fatin Medina-O’Donnell, Marta Lupiáñez, José A. Justicia, José Alvarez-Manzaneda Roldán, Ramón Jesús Reyes-Zurita, Fernando J. Alvarez-Manzaneda, Enrique Chahboun, Rachid Synthesis and Biological Evaluation of Cassane Diterpene (5α)-Vuacapane-8(14), 9(11)-Diene and of Some Related Compounds |
| title | Synthesis and Biological Evaluation of Cassane Diterpene (5α)-Vuacapane-8(14), 9(11)-Diene and of Some Related Compounds |
| title_full | Synthesis and Biological Evaluation of Cassane Diterpene (5α)-Vuacapane-8(14), 9(11)-Diene and of Some Related Compounds |
| title_fullStr | Synthesis and Biological Evaluation of Cassane Diterpene (5α)-Vuacapane-8(14), 9(11)-Diene and of Some Related Compounds |
| title_full_unstemmed | Synthesis and Biological Evaluation of Cassane Diterpene (5α)-Vuacapane-8(14), 9(11)-Diene and of Some Related Compounds |
| title_short | Synthesis and Biological Evaluation of Cassane Diterpene (5α)-Vuacapane-8(14), 9(11)-Diene and of Some Related Compounds |
| title_sort | synthesis and biological evaluation of cassane diterpene (5α)-vuacapane-8(14), 9(11)-diene and of some related compounds |
| topic | natural products semisynthesis cassane diterpenoids anti-inflammatory activity anti-cancer activity |
| url | http://hdl.handle.net/10835/13934 |
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