Synthesis and evaluation of cytotoxic effects of novel α-methylenelactone tetracyclic diterpenoids

Semi-Synthesis of Kaurenoic Acid Derivatives and Their In Vitro Cytotoxic Activities

“…The results of the cytotoxicity assays indicated that compound 1, without the α,β-unsaturated ketone, was inactive, while the 15 derivatives, which do contain this moiety, were active against all or some of the cell lines. Thus, as proposed in the literature [12,13], the α,β-unsaturated ketone is the active center, possibly acting as an alkylation site. Compound 3 without a substitution at the C-4 position had moderate activities to SGC-7901 and K562 with IC 50 values ranging from 7.37 to 7.53 µM, while compounds 5-14, 17-19, and 24 with a substitution at the C-4 position showed stronger inhibitory activity than compound 3 to those tumor cell lines with IC 50 values ranging from 0.25 to 2.47 µM.…”

“…Compound 3 has been reported previously [14], while the 14 derivatives (5-14, 17-19, 24) were reported here for the first time. The structures of the derivatives were confirmed by 1 H-NMR, 13 C-NMR, IR, HR-MS, EI-MS, and ESI-MS data (see Supporting Information). The cytotoxic activities of compound 1 and its 15 semi-synthesis derivatives were assessed on eight human cell lines (l " Table 1).…”

“…A conversion of the 15-hydroxy group of kaurenoic acid to a ketone is made in order to incorporate an α,β-unsaturated ketone into the ent-kaurane skeleton. It is well know that a main structural determinant for cytotoxicity is present in an α,β-unsaturated ketone system [12,13], which likely serves as an alkylating center and can be part of an ester, ketone, or lactone moiety. We also report several transformations on the carboxylic acid group at the C-4 position.…”

“…H-NMR and13 C-NMR spectra were recorded on a Bruker AVANCE III spectrometer using TMS as the internal standard and CDCl 3 as the solvent, reported in Oxo-kaurenoic acid ethyl ester(11): amorphous solid (27 % yield), m. p. 148.5-149.6°C; [α] D 24 : − 14.5 (CHCl 3 , c 0.10); IR: (KBr) ν max = 3426, 2950, 2926, 1728, 1692, 1452, 1245 cm −1 ; HR-ESI-MS: [M + Na] + m/z = 367.2253 (calcd. for C 22 H 32 O 3 Na: 367.2249); EI-MS: m/z (rel.…”

NO and HNO donors, nitrones, and nitroxides: Past, present, and future

“…87 The tetracyclic diterpenoid isosteviol ( Fig. 3) has attracted considerable interest due to its broad spectrum of biological activities, [89][90][91] and was thus used as scaffold for the development of • NO donors. 92 Biological screening identified compound 20 (Table 1) as a potent antiproliferative compound on B16F10 cells (ED 50 = 0.016 ± 0.004 M), a significant increase over isosteviol (ED 50 ˃ 100 M).…”