2221-81-0Relevant articles and documents
Synthesis and biological evaluation of parthenolide derivatives with reduced toxicity as potential inhibitors of the NLRP3 inflammasome
Chen, Hao,Hu, Wenhui,Ou, Yitao,Sun, Ping,Wu, Dan,Wu, Nannan,Yang, Zhongjin
, (2020)
Parthenolide (PTL) can target NLRP3 inflammasome to treat inflammation and its related disease, but its cytotoxicity limits further development as an anti-inflammatory drug. A series of PTL analogs and their Michael-type adducts were designed and synthesi
Synthesis of Active Strigolactone Analogues Based on Eudesmane- And Guaiane-Type Sesquiterpene Lactones
Cala, Antonio,Macías, Francisco A.,Molinillo, José M. G.,R. Mejías, Francisco J.,Rial, Carlos,Varela, Rosa M.,Zorrilla, Jesús G.
, p. 9636 - 9645 (2020/10/18)
Strigolactones are natural products that are exuded by plants and stimulate parasitic weed germination. Their use in herbicides is limited since they are produced in small quantities, but the synthesis of bioactive analogues provides an alternative source. In this work, eleven analogues have been synthesized. Among them, nine compounds belong to a novel family named eudesmanestrigolactones. The procedure is short (3-6 steps), the starting materials are isolated on a multigram scale, and global yields are up to 8%, which significantly enhance isolated yields. In bioassay, the compounds germinated high percentages of Phelipanche ramosa, Orobanche cumana, and Orobanche crenata seeds, even at nanogram doses (100 nM). Bioactivity was stereochemistry-dependent, and it was discussed in terms of the presence and geometry of the enol ether, orientation of the butenolide, and unsaturation of ring A. The reported compounds provide a set of readily obtained allelochemicals with potential applications as preventive herbicides.
Inhibition of TNF- α -Induced Inflammation by Sesquiterpene Lactones from Saussurea lappa and Semi-Synthetic Analogues
Choodej, Siwattra,Pudhom, Khanitha,Mitsunaga, Tohru
, p. 329 - 335 (2017/10/11)
We investigated the tumor necrosis factor-alpha (TNF- α) inhibitory activity of sesquiterpenes from Saussurea lappa root extracts. According to the hexane and EtOAc extracts showing significant activity with IC 50 values of 0.5 and 1.0 μg/mL, respectively, chromatographic fractionation of the extracts was performed and led to the isolation of 10 sesquiterpenes (1 - 10). Costunolide (1), a major compound, and dehydrocostus lactone (4) exhibited high efficiency in decreasing TNF- α levels, with IC 50 values of 2.05 and 2.06 μM, respectively. In addition, sesquiterpene analogues were synthesized to establish their structure-activity relationship (SAR) profile. Among the semi-synthetic analogues, compounds 6a and 16 showed the most potent activity with IC 50 values of 1.84 and 1.97 μM, respectively. More importantly, compound 6a showed less toxicity than costunolide and 16. These results provided the first SAR profile of sesquiterpene lactones and indicated that the α -methylene- γ -lactone moiety plays a crucial role in TNF- α inhibition. Additionally, the epoxide derivative 6a might represent a lead compound for further anti-TNF- α therapies, owing to its potent activity and reduced toxicity.
