Highly Oxidized Germacranolides from Elephantopus tomentosus and the Configurational Revision of Some Previously Reported Analogues

Abstract

Highly oxidized germacranolides are mainly found in the genus Elephantopus, contain a characteristic ten-membered molecular core that is highly flexible, and exhibit potential cytotoxic properties. However, their configurations were assigned ambiguously in previous reports due to spectroscopic observation of macrocyclic systems. Herein, 17 highly oxidized germacranolides, including 12 new germacranolides (1−12), were isolated from Elephantopus tomentosus. Their structures were characterized by spectroscopic data analysis combined with X-ray crystallography and ECD calculations, and it was possible to propose configurational revisions of five previously reported analogues (13−17). Cytotoxic activities for 1−17 against two hepatocellular carcinoma cell lines (HepG2 and Hep3B) were tested, and compounds 1−10 and 13−16 generated IC 50 values of 2.2−9.8 μM. Furthermore, the observed cytotoxic activity of 1 was determined as being mediated by inducing the apoptosis of HepG2 and Hep3B cells via mitochondrial dysfunction.

Isatin-based spiro indolenine alkaloids from Isatis indigotica Fortune with anti-neuroinflammatory and acetylcholinesterase inhibitory effects

“…Conformational analysis of the isolated compounds was carried out with the MMFF94 force field in CONFLEX software. 33,34 All obtained conformers were screened based on the energy of optimized structures at the B3LYP/6-31G(d) level with an energy window of 10 kcal mol −1 using the Gaussian 09 program package. 35 The theoretical ECD calculations of the conformations of compounds were performed with the TDDFT method at the B3LYP/6-311++G(2d,p) level with the CPCM model in methanol solution.…”

Stereochemical investigations of bioactive dihydrobenzofuran-type lignanamides from Solanum lyratum: chiral resolution, in vitro and in silico profiling

“…The NMR and ECD calculations were performed according to the previously described methods. 23–26 In general, conformational analyses were carried out via random searches in CONFLEX software using the MMFF94 force field, and all structures were optimized at the B3LYP/6-31G(d) level in the Gaussian 09 software (Gaussian Inc., Wallingford, CT, USA). 27–29…”

“…The NMR and ECD calculations were performed according to the previously described methods. [23][24][25][26] In general, conformational analyses were carried out via random searches in CON-FLEX software using the MMFF94 force field, and all structures were optimized at the B3LYP/6-31G(d) level in the Gaussian 09 software (Gaussian Inc., Wallingford, CT, USA). [27][28][29] In the ECD calculations, the conformers with a Boltzmannpopulation of over 5% were chosen and initially optimized at the B3LYP/6-311+G(d,p) level using the PCM model in MeOH solution.…”

Four Pairs of Neuroprotective Aryldihydronaphthalene‐Type Lignanamide Enantiomers from the Herbs of Solanum lyratum

“…The ECD calculations were performed according to the previously described methods [29–32] . In general, conformational analyses were carried out via random searching in CONFLEX software using the MMFF94 force field, and all structures were optimized at the B3LYP/6‐31G(d) level in the Gaussian 09 software [33–35]…”

“…The ECD calculations were performed according to the previously described methods. [29][30][31][32] In general, conformational analyses were carried out via random searching in CONFLEX software using the MMFF94 force field, and all structures were optimized at the B3LYP/ 6-31G(d) level in the Gaussian 09 software. [33][34][35] In the ECD calculations, the conformers with Boltzmann-population of over 5 % were chosen and initially optimized at the PBE0/6-311 + + G(2d,p)//B3LYP/6-31G(d) level using the PCM model in MeOH solution.…”