Sulfonamide chalcone as a new class of α-glucosidase inhibitors

Seo, Woo Duck; Kim, Jin Hyo; Kang, Jae Eun; Ryu, Hyung Won; Long, Marcus J. C.; Lee, Hyun Sun; Yang, Min; Park, Ki Hun

doi:10.1016/j.bmcl.2005.08.087

Cited by 145 publications

(83 citation statements)

References 36 publications

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“…IL-TMP activity is dependent upon N-glycosylation of asparagines within its EC2 loop. 26 TSAHC was originally found to inhibit ␣-glucosidase (median inhibitory concentration [IC 50 ] ϭ 0.98 M) 18 more strongly than sugar-derived glucosidase inhibitors currently used for therapeutic purposes, such as voglibose (IC 50 ϭ 23.4 M) and deoxynojirimycin (IC 50 ϭ 3.5 M). 27,28 Glycosidases are elevated in the interstitial fluid of tumors and sera of tumor patients and correlate with increased metastatic potential.…”

Section: Discussionmentioning

confidence: 99%

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Blockade of four-transmembrane L6 family member 5 (TM4SF5)-mediated tumorigenicity in hepatocytes by a synthetic chalcone derivative

et al. 2008

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We previously reported that the four-transmembrane L6 family member 5 (TM4SF5) was highly expressed in hepatocarcinoma, induced morphological elongation and epithelialmesenchymal transition, and caused abnormal cell growth in multilayers in vitro and tumor formation in vivo. In this study, we identified a synthetic compound, 4 -(p-toluenesulfonylamido)-4-hydroxychalcone (TSAHC) that antagonized both the TM4SF5-mediated multilayer growth and TM4SF5-enhanced migration/invasion. TSAHC treatment induced multilayer-growing cells to grow in monolayers, recovering contact inhibition without accompanying apoptosis, and inhibited chemotactic migration and invasion. E pithelial monolayer integrity is maintained by integrin-mediated cell adhesion between the cell and the extracellular matrix (ECM) and by E-cadherin-mediated contact between adjacent cells. 1 Epithelial-mesenchymal transition (EMT) through loss of cellcell contacts disrupts monolayer integrity and alters cell-ECM interactions. 2 Tumor cells disseminated from primary tumors via loss of cell adhesion and contact can migrate to and invade distal tissues. 3 We recently reported that TM4SF5-mediated EMT results in a loss of contact inhibition and multilayer growth. 4 Therefore, altered cell adhesion and contact may lead to both a loss of contact inhibition and a dissemination of metastatic cells from the primary tumor. 5 Integrin-mediated cell adhesion reorganizes actin filaments 6 through activation of diverse intracellular signaling molecules, including focal adhesion kinase (FAK), Rho guanosine triphosphatases (RhoA, Rac1, and CDC42), and others, 7 which are critical for cellular morphology and migration. 8 TM4SF proteins (i.e., tetraspanins or tetraspans) are a group of membrane proteins with four transmembrane

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Section: Discussionmentioning

confidence: 99%

“…17 TSAHC Synthesis. TSAHC (C 22 H 19 NO 4 S), synthesized as described, 18 is yellowish solid (melting point, 145°C) and stable (Ͼ98%) in DMSO for 8 weeks at room temperature and 45°C. Its purity was confirmed by high-performance liquid chromatography (HPLC) analysis using a Spheri-5 in RP-18 column (PerkinElmer).…”

Section: Methodsmentioning

confidence: 99%

Blockade of four-transmembrane L6 family member 5 (TM4SF5)-mediated tumorigenicity in hepatocytes by a synthetic chalcone derivative

et al. 2008

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“…Suppression of TM4SF5 or treatment with an anti-TM4SF5 reagent (TSAHC) or a FAK inhibitor attenuated TM4SF5/FAK interactionmediated FAK phosphorylation and activation. TSAHC was originally screened as an a-glycosidase inhibitor (Seo et al, 2005) and appears to affect the structural integrity or Nglycosylation (at N138/N155) of the extracellular loop 2 (EC2) within TM4SF5, which appears to be important for multilayer growth and migration (Lee et al, 2009b). TSAHC or FAK inhibitor treatment attenuated the interaction between TM4SF5 and FAK, indicating that both the structural aspects of the extracellular region of TM4SF5 and the activity of intracellular FAK are able to modulate the interaction between TM4SF5 and FAK.…”

Section: Tm4sf5 Activates Fak For Migration 5969mentioning

confidence: 99%

Tetraspan TM4SF5-dependent direct activation of FAK and metastatic potential of hepatocarcinoma cells

Jung¹,

Choi²,

Jang

et al. 2012

Journal of Cell Science

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SummaryTransmembrane 4 L six family member 5 (TM4SF5) plays an important role in cell migration, and focal adhesion kinase (FAK) activity is essential for homeostatic and pathological migration of adherent cells. However, it is unclear how TM4SF5 signaling mediates the activation of cellular migration machinery, and how FAK is activated during cell adhesion. Here, we showed that direct and adhesiondependent binding of TM4SF5 to FAK causes a structural alteration that may release the inhibitory intramolecular interaction in FAK. In turn, this may activate FAK at the cell's leading edge, to promote migration/invasion and in vivo metastasis. TM4SF5-mediated FAK activation occurred during integrin-mediated cell adhesion. TM4SF5 was localized at the leading edge of the cells, together with FAK and actin-organizing molecules, indicating a signaling link between TM4SF5/FAK and actin reorganization machinery. Impaired interactions between TM4SF5 and FAK resulted in an attenuated FAK phosphorylation (the signaling link to actin organization machinery) and the metastatic potential. Our findings demonstrate that TM4SF5 directly binds to and activates FAK in an adhesiondependent manner, to regulate cell migration and invasion, suggesting that TM4SF5 is a promising target in the treatment of metastatic cancer.

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“…The sulfonylamido chalcone products were obtained by through condensation of the sulfonated aminoacetophenone derivatives and hydroxybenzaldehyde, according to previously reports. 14,15 However, ASAHC was additionally reduced from nitro group to amino group. The corresponding nitro-substituted species of ASAHC was refluxed with Fe powder in acetic acid.…”

confidence: 99%

Differential inhibition of transmembrane 4 L six family member 5 (TM4SF5)-mediated tumorigenesis by TSAHC and sorafenib

Lee¹,

Lee²,

Ryu³

et al. 2011

Cancer Biology & Therapy

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Sulfonamide chalcone as a new class of α-glucosidase inhibitors

Cited by 145 publications

References 36 publications

Blockade of four-transmembrane L6 family member 5 (TM4SF5)-mediated tumorigenicity in hepatocytes by a synthetic chalcone derivative

Blockade of four-transmembrane L6 family member 5 (TM4SF5)-mediated tumorigenicity in hepatocytes by a synthetic chalcone derivative

Tetraspan TM4SF5-dependent direct activation of FAK and metastatic potential of hepatocarcinoma cells

Differential inhibition of transmembrane 4 L six family member 5 (TM4SF5)-mediated tumorigenesis by TSAHC and sorafenib

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