Design, synthesis and biological activities of 2,3-dihydroquinazolin-4(1H)-one derivatives as TRPM2 inhibitors

Zhang, Han; Liu, Huan; Luo, Xiaoling; Wang, Yuxi; Liu, Yuan; Jin, Hongwei; Liu, Zhenming; Yang, Wei; Yu, Peilin; Zhang, Liangren; Zhang, Lihe

doi:10.1016/j.ejmech.2018.04.045

Cited by 39 publications

(29 citation statements)

References 42 publications

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“…We were prompted to further investigate involvement of the TRPM2 channel in mediating SiNPs-induced epithelial cell inflammation. We started with using compound A1, a TRPM2 channel selective inhibitor developed by our own lab [44]. Western blotting analysis demonstrates TRPM2 protein expression in BEAS-2B ( Fig.…”

Section: Trpm2 Channel Activation Mediates Sinps-induced Inflammationmentioning

confidence: 99%

Silica nanoparticles induce lung inflammation in mice via ROS/PARP/TRPM2 signaling-mediated lysosome impairment and autophagy dysfunction

et al. 2020

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Background: Wide applications of nanoparticles (NPs) have raised increasing concerns about safety to humans. Oxidative stress and inflammation are extensively investigated as mechanisms for NPs-induced toxicity. Autophagy and lysosomal dysfunction are emerging molecular mechanisms. Inhalation is one of the main pathways of exposing humans to NPs, which has been reported to induce severe pulmonary inflammation. However, the underlying mechanisms and, more specifically, the interplays of above-mentioned mechanisms in NPs-induced pulmonary inflammation are still largely obscure. Considered that NPs exposure in modern society is often unavoidable, it is highly desirable to develop effective strategies that could help to prevent nanomaterials-induced pulmonary inflammation. Results: Pulmonary inflammation induced by intratracheal instillation of silica nanoparticles (SiNPs) in C57BL/6 mice was prevented by PJ34, a poly (ADP-ribose) polymerase (PARP) inhibitor. In human lung bronchial epithelial (BEAS-2B) cells, exposure to SiNPs reduced cell viability, and induced ROS generation, impairment in lysosome function and autophagic flux. Inhibition of ROS generation, PARP and TRPM2 channel suppressed SiNPs-induced lysosome impairment and autophagy dysfunction and consequent inflammatory responses. Consistently, SiNPs-induced pulmonary inflammation was prevented in TRPM2 deficient mice.

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Section: Trpm2 Channel Activation Mediates Sinps-induced Inflammationmentioning

confidence: 99%

Silica nanoparticles induce lung inflammation in mice via ROS/PARP/TRPM2 signaling-mediated lysosome impairment and autophagy dysfunction

et al. 2020

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“…N-(p-amylcinnamoyl) anthranilic acid, an inhibitor of TRPM2, inhibits H 2 O 2 -induced Ca 2+ increase in the INS-1E cells [29]. Newer, more potent inhibitors of TRPM2 are curcumin, JNJ-28583113, some derivatives of 2,3-dihydroquinazolin-4(1H)-one, scalaradial, and 12-deacetylscalaradial [44][45][46][47]. JNJ-28583113 inhibits human TRPM2 with IC 50 of 126 nM, scalaradial inhibits with IC 50 of 210 nM, and the most potent derivative of 2,3-dihydroquinazolin-4(1H)-one inhibits with IC 50 of 3.7 µM.…”

Section: Trpm2mentioning

confidence: 99%

Molecular Regulations and Functions of the Transient Receptor Potential Channels of the Islets of Langerhans and Insulinoma Cells

Islam

2020

Cells

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Insulin secretion from the β-cells of the islets of Langerhans is triggered mainly by nutrients such as glucose, and incretin hormones such as glucagon-like peptide-1 (GLP-1). The mechanisms of the stimulus-secretion coupling involve the participation of the key enzymes that metabolize the nutrients, and numerous ion channels that mediate the electrical activity. Several members of the transient receptor potential (TRP) channels participate in the processes that mediate the electrical activities and Ca2+ oscillations in these cells. Human β-cells express TRPC1, TRPM2, TRPM3, TRPM4, TRPM7, TRPP1, TRPML1, and TRPML3 channels. Some of these channels have been reported to mediate background depolarizing currents, store-operated Ca2+ entry (SOCE), electrical activity, Ca2+ oscillations, gene transcription, cell-death, and insulin secretion in response to stimulation by glucose and GLP1. Different channels of the TRP family are regulated by one or more of the following mechanisms: activation of G protein-coupled receptors, the filling state of the endoplasmic reticulum Ca2+ store, heat, oxidative stress, or some second messengers. This review briefly compiles our current knowledge about the molecular mechanisms of regulations, and functions of the TRP channels in the β-cells, the α-cells, and some insulinoma cell lines.

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“…This yielded 5-bromo 3b (Table 3, entry 13 ). However, with 2 equivalents of liquid bromine we obtained 2-amino-4,6 dibromo-benzamide 13 (Table 3, entry 14 ) 30 . This is the first report of decarboxylation of isatoic anhydride with a halogen.…”

Section: Scope Of Substituted Anilines Originating From Iaamentioning

confidence: 99%

Green Synthesis of Substituted Anilines and Quinazolines from Isatoic Anhydride-8-amide

Gondi

Bera

Westover

2019

Sci Rep

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Synthetic methods used to generate substituted anilines and quinazolines, both privileged pharmacological structures, are cumbersome, hazardous or, in some cases, unavailable. We developed a straightforward method for making isatoic anhydride-8-amide from isatin-7-carboxylic acid as a tool to easily produce a range of quinazoline and substituted aniline derivatives using adaptable pH-sensitive cyclization chemistry. The approaches are inexpensive, simple, fast, efficient at room temperature and scalable, enabling the synthesis of both established and new quinazolines and also highly substituted anilines including cyano derivatives.

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Design, synthesis and biological activities of 2,3-dihydroquinazolin-4(1H)-one derivatives as TRPM2 inhibitors

Cited by 39 publications

References 42 publications

Silica nanoparticles induce lung inflammation in mice via ROS/PARP/TRPM2 signaling-mediated lysosome impairment and autophagy dysfunction

Silica nanoparticles induce lung inflammation in mice via ROS/PARP/TRPM2 signaling-mediated lysosome impairment and autophagy dysfunction

Molecular Regulations and Functions of the Transient Receptor Potential Channels of the Islets of Langerhans and Insulinoma Cells

Green Synthesis of Substituted Anilines and Quinazolines from Isatoic Anhydride-8-amide

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