66726-11-2Relevant articles and documents
Synthesis and in vitro cytotoxic activity of semisynthetic derivatives in the santonin series
Rossi,Ambrogi,Grandolini,Scarcia,Furlani
, p. 784 - 789 (1986)
The synthesis of two new santonin derivatives namely 3-oxo-6βH-11β-phenylselenoeudesm-1,4-dien-6,13-olide (13) and 3-oxo-6β-H-eudesm-1,4,11-trien-6,13-olide (14) is reported along with the results of a series of santonins tested for activity against the g
Discovery of Potent Small-Molecule Inhibitors of Ubiquitin-Conjugating Enzyme UbcH5c from α-Santonin Derivatives
Chen, Hao,Wu, Guozhen,Gao, Shuang,Guo, Ruihua,Zhao, Zeng,Yuan, Hu,Liu, Shanxiang,Wu, Jian,Lu, Xiaolong,Yuan, Xing,Yu, Zongmin,Zu, Xianpeng,Xie, Ning,Yang, Niao,Hu, Zhenlin,Sun, Qingyan,Zhang, Weidong
, p. 6828 - 6852 (2017)
As a therapeutic target for antitumor necrosis factor (TNF)-α interventions, UbcH5c is one of the key ubiquitin-conjugating enzymes catalyzing ubiquitination during TNF-α-triggered nuclear factor kappa B (NF-κB) activation. In the present study, three series of analogues were designed and synthesized from α-santonin, and their UbcH5c inhibitory activities were screened by Western blotting and NF-κB luciferase assay. Further BIAcore, in-gel fluorescence imaging, and immunoprecipitation assays demonstrated that compound 6d exhibited robust and specific inhibition of UbcH5c, exceeding that of the positive compound 1 (IJ-5). Mechanistic investigations revealed that compound 6d preferentially bound to and inactivated UbcH5c by forming a covalent adduct with its active site Cys85. Furthermore, compound 6d exhibited potent anti-inflammatory activity against complete Freund's adjuvant-induced adjuvant arthritis in vivo. These findings suggest that the novel α-santonin-derived UbcH5c inhibitor 6d is a promising lead compound for the development of new antirheumatoid arthritis (RA) agent.
Design, synthesis and anticancer activity of Michael-type thiol adducts of α-santonin analogue with exocyclic methylene
Khazir, Jabeena,Riley, Darren L.,Chashoo, Gousia,Mir, Bilal Ahmad,Liles, David,Islam, Md. Ataul,Singh, Shashank K.,Vishwakarma, Ram A.,Pilcher, Lynne A.
, p. 769 - 779 (2015)
Abstract A series of Michael-type analogues were generated on the C-ring of α-santonin (α-methylene-γ-butyrolactone) upon reaction with various thiols. All the thiol adducts synthesized were evaluated for their anticancer activity against four human cance
Synthesis and biological evaluation of α-santonin derivatives as anti-hepatoma agents
Chen, Hao,Yang, Xiao,Yu, Zongmin,Cheng, Ziying,Yuan, Hu,Zhao, Zeng,Wu, Guozhen,Xie, Ning,Yuan, Xing,Sun, Qingyan,Zhang, Weidong
, p. 90 - 97 (2018)
A series of α-santonin-derived compounds as potentially anti-hepatoma agents were designed and synthesized in an effort to find novel therapeutic agents. Among them, derivative 5h was more potent than the positive control 5-fluorouracil (5-Fu) on HepG-2, QGY-7703 and SMMC-7721 with IC50 values of 7.51, 3.06 and 4.08 μM, respectively. The structure-activity relationships (SARs) of these derivatives were discussed. In addition, flow cytometry and western blot assay revealed that the derivatives induced hepatoma cells apoptosis by facilitating apoptosis-related proteins expressions. Our findings suggested that these α-santonin-derived analogues hold promise as chemotherapeutic agents for the treatment of human hepatocellular cancer.
REACTIONS AFFECTING THE γ-LACTONE RING OF α-SANTONIN
Adekenov, S. M.,Gafurov, N. M.
, p. 452 - 455 (1992)
The selective dehydrogenation of the eudesmanolide α-santonin and its alkylation with the introduction of an allyl fragment into its γ-lactone ring are described.It has been established that these reactions are regio- and stereoselective.The structures of
Sesquiterpene Lactones Potentiate Olaparib-Induced DNA Damage in p53 Wildtype Cancer Cells
Osborne, Hugh C.,Larrosa, Igor,Schmidt, Christine K.
, (2022/01/22)
Despite notable advances in utilising PARP inhibitor monotherapy, many cancers are not PARP inhibitor-sensitive or develop treatment resistance. In this work, we show that the two structurally-related sesquiterpene lactones, a 2-bromobenzyloxy derivative
Combination of Pseudo-Natural Product Design and Formal Natural Product Ring Distortion Yields Stereochemically and Biologically Diverse Pseudo-Sesquiterpenoid Alkaloids
Liu, Jie,Flegel, Jana,Otte, Felix,Pahl, Axel,Sievers, Sonja,Strohmann, Carsten,Waldmann, Herbert
supporting information, p. 21384 - 21395 (2021/08/23)
We describe the synthesis and biological evaluation of a new natural product-inspired compound class obtained by combining the conceptually complementary pseudo-natural product (pseudo-NP) design strategy and a formal adaptation of the complexity-to-diversity ring distortion approach. Fragment-sized α-methylene-sesquiterpene lactones, whose scaffolds can formally be viewed as related to each other or are obtained by ring distortion, were combined with alkaloid-derived pyrrolidine fragments by means of highly selective stereocomplementary 1,3-dipolar cycloaddition reactions. The resulting pseudo-sesquiterpenoid alkaloids were found to be both chemically and biologically diverse, and their biological performance distinctly depends on both the structure of the sesquiterpene lactone-derived scaffolds and the stereochemistry of the pyrrolidine fragment. Biological investigation of the compound collection led to the discovery of a novel chemotype inhibiting Hedgehog-dependent osteoblast differentiation.
Synthesis of 6-epi-tuberiferin and the biological activities of tuberiferin, dehydrobrabrachylaenolide, 6-epi-tuberiferin, and their synthetic intermediates
Li, Dan,Higuchi, Yohsuke,Kobayashi, Takafumi,Shimoma, Fumito,Bai, Yuhua,Ando, Masayoshi
, (2021/02/02)
Tuberiferin, 6-epi-tuberifelin, dehydrobrachylaenolide and two series of eudesmanolides, eudesmane-12,6 α-lactones and eudesmane-12,6β-lactones, were synthesized for the studies of the structure–activity relationships to explore novel anti-inflammatory, a
Preparation and Phytotoxicity Evaluation of 11,13-Dehydro seco-Guaianolides
Chinchilla, Nuria,Santana, Alejandro,Varela, Rosa M.,Fronczek, Frank R.,Molinillo, José M. G.,MacIás, Francisco A.
, p. 2501 - 2508 (2019/09/30)
11,13-Dehydro seco-guaianolides, a particular type of sesquiterpene lactones, were synthesized from the commercially available α-santonin (11) using a facile strategy involving a high-yielding photochemical reaction. Natural products 10 and 17 from Artemi
Semisynthetic derivatives of sesquiterpene lactones by palladium-catalyzed arylation of the α-methylene-γ-lactone substructure
Han, Changho,Barrios, Francis J.,Riofski, Mark V.,Colby, David A.
supporting information; experimental part, p. 7176 - 7179 (2009/12/09)
(Chemical Equation Presented) The palladium-catalyzed arylation of different α-methylene-γ-lactone-containing sesquiterpene lactones was shown to produce E-olefin coupling products selectively in moderate to excellent yields. Biological evaluation of thes
