28254-53-7Relevant articles and documents
Acyl Derivatives of Eudesmanolides To Boost their Bioactivity: An Explanation of Behavior in the Cell Membrane Using a Molecular Dynamics Approach
Mejías, Francisco J. R.,Durán, Alexandra G.,Zorrilla, Jesús G.,Varela, Rosa M.,Molinillo, José M. G.,Valdivia, Manuel M.,Macías, Francisco A.
, p. 1297 - 1307 (2021/02/09)
Semisynthetic analogs of natural products provide an important approach to obtain safer and more active drugs and they can also have enhanced physicochemical properties such as persistence, cross-membrane processes and bioactivity. Acyl derivatives of different natural product families, from sesquiterpene lactones to benzoxazinoids, have been synthesized and tested in our laboratories. These compounds were evaluated against tumoral and nontumoral cell lines to identify selective derivatives with a reduced negative impact upon application. The mode of action of these compounds was analyzed by anti-caspase-3 assays and molecular dynamics simulations with cell membrane re-creation were also carried out. Aryl derivatives of eudesmanolide stand out from the other compounds and are better than current anticancer drugs such as etoposide in terms of selectivity and activity. Computational studies provide evidence that lipophilicity plays a key role and the 4-fluorobenzoyl derivative can pass easily through the cell membrane.
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.
Absolute stereostructures and syntheses of saussureamines A, B, C, D and E, amino acid-sesquiterpene conjugates with gastroprotective effect, from the roots of Saussurea lappa
Matsuda, Hisashi,Kageura, Tadashi,Inoue, Yasunao,Morikawa, Toshio,Yoshikawa, Masayuki
, p. 7763 - 7777 (2007/10/03)
From the methanolic extract of the dried roots of Saussurea lappa Clarke, Saussureae Radix, five amino acid-sesquiterpene conjugates, saussureamines A, B, C, D and E, were isolated together with a lignan glycoside, (-)-massoniresinol 4-O-β-D-glucopyranoside. Their stereostructures were determined on the basis of chemical and physicochemical evidence. In addition, saussureamines and the related amino acid-sesquiterpene conjugates were synthesized using a Michael type addition reaction of amino acid to the α-methylene-γ-lactone moiety of sesquiterpenes. Saussureamines A, B and C, costunolide and dehydrocostus lactone showed a gastroprotective effect on acidified ethanol-induced gastric mucosal lesions in rats. Saussureamines A also exhibited an inhibitory effect on gastric mucosal lesions induced by water-immersion stress in mice. (C) 2000 Elsevier Science Ltd.
