1025815-71-7Relevant academic research and scientific papers
Steric control of the nuclearity of metallamacrocycles: Formation of a hexanuclear gallium metalladiazamacrocycle and a hexadecanuclear manganese metalladiazamacrocycle
Lee, Kyungjin,John, Rohith P.,Park, Mira,Moon, Dohyun,Ri, Hyeong-Cheol,Kim, Ghyung Hwa,Lah, Myoung Soo
, p. 131 - 136 (2008)
An S6-symmetric hexanuclear gallium metalladiazamacrocycle, [GaIII6L26S6] with a -(ΛΔ)(ΛΔ)- chiral sequence and an S 8-symmetric hexadecanuclear manganese metalladiazamacrocycle,
Senolytic activity of piperlongumine analogues: Synthesis and biological evaluation
Liu, Xingui,Wang, Yingying,Zhang, Xuan,Gao, Zhengya,Zhang, Suping,Shi, Peizhong,Zhang, Xin,Song, Lin,Hendrickson, Howard,Zhou, Daohong,Zheng, Guangrong
supporting information, p. 3925 - 3938 (2018/06/19)
Selective clearance of senescent cells (SCs) has emerged as a potential therapeutic approach for age-related diseases, as well as chemotherapy- and radiotherapy-induced adverse effects. Through a cell-based phenotypic screening approach, we recently identified piperlongumine (PL), a dietary natural product, as a novel senolytic agent, referring to small molecules that can selectively kill SCs over normal or non-senescent cells. In an effort to establish the structure-senolytic activity relationships of PL analogues, we performed a series of structural modifications on the trimethoxyphenyl and the α,β-unsaturated δ-valerolactam rings of PL. We show that modifications on the trimethoxyphenyl ring are well tolerated, while the Michael acceptor on the lactam ring is critical for the senolytic activity. Replacing the endocyclic C2–C3 olefin with an exocyclic methylene at C2 render PL analogues 47–49 with increased senolytic activity. These α-methylene containing analogues are also more potent than PL in inducing ROS production in WI-38 SCs. Similar to PL, 47–49 reduce the protein levels of oxidation resistance 1 (OXR1), an important oxidative stress response protein that regulates the expression of a variety of antioxidant enzymes, in cells. This study represents a useful starting point toward the discovery of senolytic agents for therapeutic uses.
Piperlongumine (piplartine) and analogues: Antiproliferative microtubule-destabilising agents
Meegan, Mary J.,Nathwani, Seema,Twamley, Brendan,Zisterer, Daniela M.,O'Boyle, Niamh M.
, p. 453 - 463 (2016/10/04)
Piperlongumine (piplartine, 1) is a small molecule alkaloid that is receiving intense interest due to its antiproliferative and anticancer activities. We investigated the effects of 1 on tubulin and microtubules. Using both an isolated tubulin assay, and a combination of sedimentation and western blotting, we demonstrated that 1 is a tubulin-destabilising agent. This result was confirmed by immunofluorescence and confocal microscopy, which showed that microtubules in MCF-7 breast cancer cells were depolymerized when treated with 1. We synthesised a number of analogues of 1 to explore structure-activity relationships. Compound 13 had the best cytotoxic profile of this series, showing potent effects in human breast carcinoma MCF-7?cells whilst being relatively non-toxic to non-tumorigenic MCF-10a cells. These?compounds will be further developed as potential clinical candidates for the treatment of breast cancer.
Rhodium-catalyzed decarbonylative direct olefination of arenes with vinyl carboxylic acids
Qiu, Ruiying,Zhang, Lingjuan,Xu, Conghui,Pan, Yixiao,Pang, Hongze,Xu, Lijin,Li, Huanrong
supporting information, p. 1229 - 1236 (2015/04/22)
A rhodium(I)-catalyzed direct C-H bond olefination of pyridyl-substituted arenes with readily available vinyl carboxylic acids has been realized. This reaction occurred efficiently without the need for any external oxidant, affording the ortho-olefinated products in high yields and excellent regioselectivities. Diversely substituted vinyl carboxylic acids behaved as efficient olefination reagents under the reaction conditions, and a range of functional groups in both coupling partners was well tolerated. Mechanistic studies indicated that a decarbonylation step is involved in this catalytic process, and pivalic anhydride [(t-BuCO)2O] acts as the activator of the carboxylic acids for the in situ generation of highly active anhydrides.
Rational Design of Highly Diastereoselective, Organic Base-Catalyzed, Room-Temperature Michael Addition Reactions
Soloshonok, Vadim A.,Cai, Chaozhong,Hruby, Victor J.,Van Meervelt, Luc,Yamazaki, Takashi
, p. 6688 - 6696 (2007/10/03)
Via the rational design of a single-preferred transition state, stabilized by electron donor - acceptor-type attractive interactions, structural and geometric requirements for the corresponding starting compounds have been determined. The Ni(II) complex of the Schiff base of glycine with o-[N-α-picolylamino]acetophenone, as a nucleophilic glycine equivalent, and N-(trans-enoyl)oxazolidin-2-ones, as derivatives of an α,β-unsaturated carboxylic acid, were found to be the substrates of choice featuring geometric/conformational homogeneity and high reactivity. The corresponding Michael addition reactions were found to proceed at room temperature in the presence of catalytic amounts of DBU to afford quantitatively the addition products with virtually complete diastereoselectivity. Acidic decomposition of the products followed by treatment of the reaction mixture with NH4OH gave rise to the diastereomerically pure 3-substituted pyroglutamic acids.
