- Structure-activity relationship and mechanistic study on guggulsterone derivatives; Discovery of new anti-pancreatic cancer candidate
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Pancreatic cancer is one of the deadliest types of malignancies. A new intervention aiming to combat pancreatic cancer is targeting its extra-ordinary ability to tolerate nutrition starvation, a phenomenon known as “Austerity”. As a part of a research program aiming to develop a new-generation of anticancer agents, known as “anti-austerity agents”, guggulsterone derivatives (GSDs) were identified as unique anti-austerity agents in terms of potency and selectivity. These agents are able to exert preferential cytotoxic activity only under nutrient-deprived conditions with little or no toxicity under normal conditions. In the present study, a library of 14 GSDs was synthesized and screened against PANC-1 human pancreatic cells. Among tested compounds, GSD-11 showed the most potent activity with PC50 a value of 0.72 μM. It also inhibited pancreatic cancer cell migration and colony formation in a concentration-dependent manner. A mechanistic study revealed that this compound can inhibit the activation of the Akt/mTOR signaling pathway. Therefore, GSD-11 could be a promising lead compound for the anticancer drug discovery against pancreatic cancer.
- Kohyama, Aki,Kim, Min Jo,Yokoyama, Rei,Sun, Sijia,Omar, Ashraf M.,Phan, Nguyen Duy,Meselhy, Meselhy R.,Tsuge, Kiyoshi,Awale, Suresh,Matsuya, Yuji
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supporting information
(2021/12/24)
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- Ruthenium acetate complexes as versatile probes of metal-ligand interactions: Insight into the ligand effects of vinylidene, carbene, carbonyl, nitrosyl and isocyanide
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Reaction of cis-Ru(2-OAc)2(PPh3) 2 with two-electron donor ligands L results in the formation of complexes trans-[Ru(1-OAc)(2-OAc)L(PPh3) 2] (L = CO, NO+, CNtBu). Vinylidene complexes (L = C=CHR) may be prepared from the corresponding reaction with terminal alkynes HC=CR, and species containing hydroxyvinylidene ligands (L = C=CHCR1R 2{OH}) may be prepared from related reactions with propargyl alcohols HC=CCR1R2{OH}. Treatment of cis-Ru(κ2- OAc)2(PPh3)2 with ω-alkynols HC=C(CH 2)nOH (n = 2-4) results in the formation of oxacyclocarbene complexes [L = CCH2(CH2)nO]. An analysis of the spectroscopic data and the structural metrics (as determined by X-ray crystallography) of this series of complexes allows for the relative donor/acceptor properties of the ligand L to be evaluated. This comparison indicates that the vinylidene ligand behaves in a similar fashion to the isocyanide ligand. The complex cis-[Ru(2-OAc)2(PPh 3)2] acts as a precursor for the formation of the complexes trans-[Ru(1-OAc)(2-OAc)L(PPh3) 2] where L is a two-electron donor, σ-donor/π-acceptor ligand. The structural and spectroscopic data of these species provide insight into the relative electron demand of the ligands L.
- Welby, Christine E.,Eschemann, Thomas O.,Unsworth, Christopher A.,Smith, Elizabeth J.,Thatcher, Robert J.,Whitwood, Adrian C.,Lynam, Jason M.
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experimental part
p. 1493 - 1506
(2012/06/16)
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- 17-Methyleneandrostan-3alpha-ol analogs as CRH inhibitors
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17-Methyleneandrostan-3α-ol analogs are useful as corticotropin releasing hormone (CRH) inhibitors, and especially as anti-depressants, when administered to the vomeronasal organ. An improved synthesis of 17-methylenandrost-4-en-3α-ol is disclosed.
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