1196-28-7Relevant articles and documents
HHQ-4, a quinoline derivate, preferentially inhibits proliferation of glucose-deprived breast cancer cells as a GRP78 down-regulator
Xiao, Xiao,Li, Shuo,Zhang, Xiaoxun,Lu, Jinjian,Wang, Weiguang,Zhou, Shijia,Zhang, Jingyao,Wang, Rui,Li, Ao
, p. 10 - 25 (2019)
As a central regulator for endoplasmic reticulum (ER)stress, glucose-regulated protein 78 (GRP78), controls the activation of ER-transmembrane signaling mechanisms by inducing unfolded protein response (UPR)in response to ER stress. Although limited glucose availability often occurs in poorly vascularized solid cancers, cancer cells often initiate the UPR to support cellular homeostasis and survival under stress conditions. Therefore, targeting GRP78 expression and UPR pathway activation may provide a new strategy for anticancer therapy. Based on this premise, we investigated the molecular mechanisms of a synthetic quinolone derivative, 2-hexyl-3-methyl-4(1H)-quinolinone (HHQ-4), in regulating the GRP78 expression and UPR transcriptional program under glucose deprivation or 2-deoxy-D-glucose (2-DG)-stressed conditions. We found that HHQ-4 suppressed the transcriptional and translational expression of GRP78 gene in glucose-deprived breast cancer cells. HHQ-4 also showed selective antiproliferative activity against glucose-deprived breast cancer cells. Constitutive expression of GRP78 completely prevented breast cancer cells from HHQ-4-mediated proliferation inhibition during glucose starvation, stressing the important role of suppression of the GRP78 in HHQ-4-mediated cell proliferation inhibition. HHQ-4 was also found to exert inhibitory activity against breast cancer cell proliferation by suppressing three survival arms of the UPR, including PERK/eIF2α/ATF4, IRE1/XBP1, and ATF6, which orchestrate an intricate signaling network to modulate GRP78 gene transcription under glucose-deprived stress. Furthermore, HHQ-4 combined with 2-DG synergistically inhibited breast cancer cell proliferation. Our findings show HHQ-4 could be a promising candidate, alone or in combination with 2-DG, for selectively inhibiting breast cancer cell proliferation by down-regulating the transcription and expression of GRP78 under stressful microenvironments.
Perfluorobutyl Iodide Mediated [1,2] and [2,3] Stevens Rearrangement for the Synthesis of Indolin-3-Ones
Chen, Zhen-Yu,Lin, Bi-Zhen,Chen, Lei,Zou, Yong,Yan, Ming,Zhang, Xue-Jing
, p. 4368 - 4372 (2020)
The tertiary amine and ketone components of 1-carbonyl-substituted anilines undergo [1,2] and [2,3] Stevens rearrangement reactions, triggered by a C4F9 radical, formed from electron donor–acceptor complexes. This approach enables the formation of a quaternary ammonium salt and thus a Stevens rearrangement to afford indolin-3-ones under mild conditions. (Figure presented.).
Ir(iii)-Catalysed electrooxidative intramolecular dehydrogenative C-H/N-H coupling for the synthesis of N-H indoles
Chang, Sukbok,Kim, Dongwook,Kim, Youyoung
supporting information, p. 12309 - 12312 (2021/12/07)
Herein, an iridium(iii)-catalysed electrooxidative intramolecular dehydrogenative C-H/N-H coupling of unprotected 2-alkenyl anilines is described. The developed method allows the synthesis of a variety of 3-substituted N-H indole scaffolds under undivided electrolytic conditions. Mechanistic studies suggest that the reaction proceeds through the electro-oxidation induced reductive elimination pathway.
Experimental and Computational Studies on Cp*CyRh(III)/KOPiv-Catalyzed Intramolecular Dehydrogenative Cross-Couplings for Building Eight-Membered Sultam/Lactam Frameworks
Li, Liping,Gao, Hui,Sun, Ming,Zhou, Zhi,Yi, Wei
supporting information, p. 5473 - 5478 (2020/07/14)
Described herein is an unusual Cp*CyRh(III)-catalyzed intramolecular site-specific aryl C-H annulation, a highly chemoselective protocol providing direct access to eight-membered sultams/lactams with broad substrate/functional group tolerance. Experimental and computational studies reveal that such a transformation involves a unique PivOH-assisted aryl C-H activation/alkene insertion/β-H elimination/hydrogen-transfer process involving the Rh(III)-hydride species as the active intermediate with the concomitant release of H2 as the major byproduct, thus enabling the developed Cp*CyRh(III) catalysis with redox-neutral and highly atom-economical features.
Profiling structural diversity and activity of 2-alkyl-4(1H)-quinoloneN-oxides ofPseudomonasandBurkholderia
B?ttcher, Thomas,Dieterich, Cora Lisbeth,Prothiwa, Michaela,Szamosvári, Dávid
supporting information, p. 6328 - 6331 (2020/06/21)
We synthesized all major saturated and unsaturated 2-alkyl-4(1H)-quinoloneN-oxides ofPseudomonasandBurkholderia, quantified their native production levels and characterized their antibiotic activities against competingStaphylococcus aureus. We demonstrate that quinolone core methylation and position of unsaturation in the alkyl-chain dictate antibiotic potency which supports the proposed mechanism of action.
