Synthesis and Biological Evaluation of Cassane Diterpene (5 alpha)-Vuacapane-8(14), 9(11)-Diene and of Some Related Compounds Zentar, Houda Jannus, Fatin Medina O'Donnell, Marta Lupiáñez Cara, José Antonio Justicia Ladrón De Guevara, José Reyes Zurita, Fernando Jesús Álvarez De Manzaneda Roldán, Enrique Chahboun Karimi, Rachid 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 mu g/mL and 5.71 +/- 0.14 mu g/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 mu g/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. 2022-09-28T11:08:27Z 2022-09-28T11:08:27Z 2022-09-04 info:eu-repo/semantics/article Zentar, H... [et al.]. Synthesis and Biological Evaluation of Cassane Diterpene (5alpha)-Vuacapane-8(14), 9(11)-Diene and of Some Related Compounds. Molecules 2022, 27, 5705. [https://doi.org/10.3390/molecules27175705] https://hdl.handle.net/10481/77050 10.3390/molecules27175705 eng http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Atribución 4.0 Internacional MDPI