Semisynthesis and Non-Small-Cell Lung Cancer Cytotoxicity Evaluation of Germacrane-Type Sesquiterpene Lactones from Elephantopus scaber

Abstract

Two series of germacrane-type sesquiterpene lactones were produced by semisynthetic modulation of scaberol C, which was prepared by a standard chemical transformation from an Elephantopus scaber extract. Their inhibition activities against non-small-cell lung cancer cells were screened, and preliminary structure−activity relationships were also established. Among them, monomeric analog 1u and dimeric analog 3d exhibited superior anti-non-small-cell lung cancer cytotoxic potencies with IC 50 values of 4.3 and 0.7 μM against A549 cells, respectively, and were more active than cisplatin and the standard sesquiterpene lactones, parthenolide and scabertopin. Further studies revealed that compounds 1u and 3d cause G2/M phase arrest and induce apoptosis through the activation of mitochondrial pathways in A549 cells. Collectively, the results obtained suggest that compounds 1u and 3d are promising anti-non-small-cell lung cancer lead compounds.

Identification of Crucial Polymethoxyflavones Tangeretin and 3,5,6,7,8,3′,4′-Heptamethoxyflavone and Evaluation of Their Contribution to Anticancer Effects of Pericarpium Citri Reticulatae ‘Chachi’ during Storage

“…Since the free PMFs were the most influential factors discriminating the types of PCR-C during storage, and they showed an increasing trend, we further purified the free PMFs in PCR-C (PCR-CF) using HPD300 resin [ 17 ] to investigate their anticancer effect. Recently, A549 cells, human alveolar epithelial cells, have been widely and universally applied to investigate the anticancer effect of natural products in NSCLC [ 25 , 26 , 27 ]. Firstly, the morphology changes of A549 cells that were treated with PCR-CF at different storage periods were observed under the inverted phase-contrast microscopy.…”

Synthesis and Bioactivity Evaluation of Nepetaefolin F and Its Analogues

“…Furthermore, triptobenzene L (7) was Esterification has been considered as a useful method to expand the diversity of candidate compounds and enhance the biological activity. 24,25 With sufficient amount of triptobenzene L (7) in hand, we next set out to streamline the synthesis of derivatives 18−42 at the diol at C3 and C19 positions in a nonselective manner with different carboxylic acids (Scheme 4). In addition, derivatives 43 and 44 were prepared by the treatment of triptobenzene L (7) with triethylamine (TEA) and methanesulfonyl chloride (MsCl) (Scheme 5).…”

“…The combined solution was concentrated under reduced pressure, and the residue was subjected to purification on silica gel chromatography and evaporated. The residue was purified by chromatography on silica gel (PE/EtOAc = 100:1) to afford 8a (8.4 g, 80%) as pale yellow oil: [α] D 25 + 27 (c 0. (1S,4aS,10aR)-7-Isopropyl-1,4a-dimethyl-1,4,4a,9,10,10ahexahydrophenanthrene-1-carbaldehyde (16).…”

“…mg, 59% brsm) as colorless oil: [α] D25 + 40 (c 1.0, CH 2 Cl 2 );1 H NMR (400 MHz, CDCl 3 ) δ 7 16. (d, J = 8.2 Hz, 1H, H-11), 7.00 (d, J = 8.2 Hz, 1H, H-12), 6.89 (s, 1H, H-14), 4.43 (d, J = 11.7 Hz, 1H, H-19), 4.24 (d, J = 11.7 Hz, 1H, H-19), 3.36 (dd, J = 11.3, 5.0 Hz, 1H, H-3), 2.94 (dd, J = 17.1, 6.2 Hz, 1H, H-7), 2.83 (m, 2H, H-7 and H-15), 2.34 (dt, J = 13.3, 3.6 Hz, 1H, H-1), 2.08 (s, 3H, OAc), 2.00 (dd, J = 13.3, 6.9 Hz, 1H, H-6), 1.91 (m, 1H, H-2), 1.86 (m, 1H, H-2), 1.78 (m, 1H, H-6), 1.56 (td, J = 13.0, 4.7 Hz, 1H, H-1), 1.48 (dd, J = 12.5, 1.9 Hz, 1H, H-5), 1.22 (s, 3H, H-18), 1.21 (d, J = 6.0 Hz, 6H, H-16 and H-17), 1.19 (s, 3H, H-20); 13 C NMR (100 MHz, CDCl 3 ) δ 171.3 (OAc), 146.1 (C-9), 146.1 (C-13), The human gastric cancer cell line MGC 803, breast cancer cell line MDA-MB-231, and ovarian carcinoma cell line SKOV-3 were obtained from Cell Bank, Type Culture Collection of Chinese Academy of Sciences (Shanghai, People's Republic of China).…”