618359-62-9Relevant academic research and scientific papers
Unambiguous Identification of β-Tubulin as the Direct Cellular Target Responsible for the Cytotoxicity of Chalcone by Photoaffinity Labeling
Zhou, Bo,Yu, Xingxin,Zhuang, Chunlin,Villalta, Peter,Lin, Yong,Lu, Junxuan,Xing, Chengguo
, p. 1436 - 1445 (2016)
Chalcone is a simple and potentially privileged structure in medicinal chemistry with a diverse repertoire of biological activities, among which cytotoxicity is of particular interest. The sharp structure–activity relationship (SAR) for chalcone's cytotoxicity suggests structure-specific target interactions. Despite the numerous putative targets proposed, evidence for direct target interactions in cells is unavailable. In this study, guided by the sharp cytotoxic SAR, we developed a cytotoxic chalcone-based photoaffinity labeling (PAL) probe, (E)-3-(3-azidophenyl)-1-[3,5-dimethoxy-4-(prop-2-yn-1-yloxy)phenyl]-2-methylprop-2-en-1-one (C95; IC50: 0.38±0.01 μm), along with two structurally similar non-cytotoxic probes. These probes were used to search for the direct cellular target responsible for chalcone's cytotoxicity through intact cell-based PAL experiments, in which β-tubulin was identified to specifically interact with the cytotoxic probe (i.e., C95) but not the non-cytotoxic probes. A set of phenotypical and biochemical assays further reinforced β-tubulin as the cytotoxic target of chalcones. Peptide mass quantitation by mass spectrometric analysis revealed one peptide potentially labeled by C95, providing information on chalcone's binding site on β-tubulin.
Synthesis and chiral HPLC analysis of the dibenzyltetrahydrofuran lignans, larreatricins, 8'-epi-larreatricins, 3,3'-didemethoxyverrucosins and meso-3,3'-didemethoxynectandrin B in the creosote bush (Larrea tridentata): evidence for regiospecific control of coupling.
Moinuddin, Syed G A,Hishiyama, Shojiro,Cho, Man-Ho,Davin, Laurence B,Lewis, Norman G
, p. 2307 - 2313 (2007/10/03)
The creosote bush (Larrea tridentata) lignans are linked via 8-8' bonds, with the simplest apparently being E-p-anol derived. Of the latter, four of the six theoretically possible diastereoisomers were isolated, namely (-)-larreatricin, (-)-8'-epi-larreatricin, meso-3,3'-didemethoxynectandrin B and the new compounds, (+)- and (-)-3,3'-didemethoxyverrucosins. Following synthesis of each in either racemic or meso form, and chiral HPLC separation of the antipodes of the racemates, it was established that naturally occurring (-)-larreatricin and (-)-8'-epi-larreatricin were present in 92 and 98% enantiomeric excess, respectively, whereas 3,3'-didemethoxyverrucosin was essentially racemic and 3,3'-didemethoxynectandrin B was in the meso-form. The evidence suggests that formation of these lignans occurs under regiospecific, rather than stereoselective, coupling control. This contrasts with laccase-catalyzed "random" coupling of E-p-anol in vitro which generates the corresponding racemic 8-8', 8-3' and 8-O-4' linked dimeric moieties.
