RT journal article
T1 Semisynthesis and Antitumour Evaluation of Natural Derivatives from ent-Kaurene ent-15α-Angeloyloxykaur-l6-en-3β-ol Isolated from Distichoselinum tenuifolium
A1 Yasser, Yass K.
A1 Gil, Daniel
A1 Zentar, Houda
A1 Durán Peña, María Jesús
A1 Prados-Lopez, Belén
A1 Juárez-Moreno, Jorge
A1 Botubol Ares, José Manuel
A1 Haidour, Ali
A1 Sainz, Juan
A1 Fernández, Antonio
A1 Álvarez Manzaneda, Ramón
A1 Chahboun, Rachid
A1 Reyes-Zurita, Fernando J.
A2 Química Orgánica
K1 antitumour activity
K1 apoptosis
K1 cell cycle
K1 Ent-kaurenes
K1 mitochondrial membrane potential
AB Two natural ent-kaurene diterpenoids, ent-15α-angeloyloxykaur-16-en-3β-ol (7) and ent-15α-angeloyloxykaur-16-en-3β,9-diol (8), were extracted from the aerial parts of Distichoselinum tenuifolium, and six new derivatives were synthesised from compound (7). The antitumour properties of these natural and derivative ent-kaurenes (2, 7, 9–13) were evaluated in three cancer cell lines: HT29 (colon cancer), HepG2 (hepatocellular carcinoma), and B16-F10 (murine melanoma). Among them, the synthesised ent-kaurene (13) containing an exomethylene–cyclopentanone moiety showed the strongest antiproliferative effects in all cell lines tested, with significantly lower IC50 values around 2.5 μM. Compounds 13 and 12, together with their precursor (7), were selected for further comparative cytometric and microscopic analyses. Cell cycle studies revealed that derivatives 12 and 13 exhibited promising cytostatic activity by inducing selective G2/M phase arrest, particularly effective in HT29 and HepG2 cells. Conversely, precursor (7) showed no significant effect on B16-F10 cell cycle distribution. The Annexin V-FITC/PI double staining assay confirmed the robust apoptotic effects of compounds (7), 12 and 13, with compound 13 inducing up to 99% total apoptosis and exhibiting significant apoptotic activity in all cell lines tested. These apoptotic effects were closely linked to mitochondrial dysfunction, as evidenced by a marked loss of mitochondrial membrane potential and reduced Rh123 fluorescence in treated cells, thereby activating the intrinsic apoptotic pathway. These findings highlight the critical role of mitochondrial disruption in the cytotoxic mechanisms of these ent-kaurenes and underscore their potential as promising anticancer agents.
PB Multidisciplinary Digital Publishing Institute (MDPI)
SN 1422-0067
YR 2024
FD 2024
LK http://hdl.handle.net/10498/36093
UL http://hdl.handle.net/10498/36093
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 05-nov-2026