Identification of N-(quinolin-8-yl)benzenesulfonamides as agents capable of down-regulating NFκB activity within two separate high-throughput screens of NFκB activation

Xie, Yuning; Deng, Shi Xian; Thomas, Craig J.; Liu, Yidong; Zhang, Ya Qin; Rinderspacher, Alison; Huang, Wenwei; Gong, Gangli; Wyler, Michael; Cayanis, E.; Aulner, Nathalie; Többen, Udo; Chung, Caty; Pampou, Sergey; Southall, Noel; Vidović, Dušica; Schürer, Stephan C.; Branden, Lars; Davis, R. Eric; Staudt, Louis M.; Inglese, James; Austin, Christopher P.; Landry, Donald W.; Smith, Dorothy; Auld, Douglas S.

doi:10.1016/j.bmcl.2007.10.100

Cited by 19 publications

(16 citation statements)

References 23 publications

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“…In addition, in situ hybridization showed that Lcn2 message was induced in scattered epithelia after inoculation (Figure 6C), typical of ICs. To further examine the interaction between UPEC and CD epithelia, we used an IC line (85,86) and applied heat-killed UPECs (5 × 10 6 CFU; P < 0.005; Figure 6D). The bacteria induced LCN2 expression in an NF-κB-sensitive fashion in the ICs (85,86).…”

Section: Figurementioning

confidence: 99%

“…To further examine the interaction between UPEC and CD epithelia, we used an IC line (85,86) and applied heat-killed UPECs (5 × 10 6 CFU; P < 0.005; Figure 6D). The bacteria induced LCN2 expression in an NF-κB-sensitive fashion in the ICs (85,86). In addition, when we explanted epithelia directly from the medulla of Lcn2-Luc2-expressing kidneys (15,43,45) and treated the cells with living UPEC (P < 0.01; Figure 6E), we visualized the activated LCN2-Luc2 reporter.…”

Section: Figurementioning

confidence: 99%

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α–Intercalated cells defend the urinary system from bacterial infection

Paragas¹,

Kulkarni²,

Werth³

et al. 2014

J. Clin. Invest.

129

111

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α-Intercalated cells (A-ICs) within the collecting duct of the kidney are critical for acid-base homeostasis. Here, we have shown that A-ICs also serve as both sentinels and effectors in the defense against urinary infections. In a murine urinary tract infection model, A-ICs bound uropathogenic E. coli and responded by acidifying the urine and secreting the bacteriostatic protein lipocalin 2 (LCN2; also known as NGAL). A-IC-dependent LCN2 secretion required TLR4, as mice expressing an LPS-insensitive form of TLR4 expressed reduced levels of LCN2. The presence of LCN2 in urine was both necessary and sufficient to control the urinary tract infection through iron sequestration, even in the harsh condition of urine acidification. In mice lacking A-ICs, both urinary LCN2 and urinary acidification were reduced, and consequently bacterial clearance was limited. Together these results indicate that A-ICs, which are known to regulate acid-base metabolism, are also critical for urinary defense against pathogenic bacteria. They respond to both cystitis and pyelonephritis by delivering bacteriostatic chemical agents to the lower urinary system.

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Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

α–Intercalated cells defend the urinary system from bacterial infection

Paragas¹,

Kulkarni²,

Werth³

et al. 2014

J. Clin. Invest.

129

111

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“…1, 133.5, 133.2, 132.0, 131.5, 131.3, 131.2, 129.4, 127.6, 127.5, 127.2, 126.7, 125.7, 120.9, 118.7. GC-MS (EI) m/z 319 (M + +2, 5), 317 (M + , 13), 218 (25), 7, 142 (64), 140 (5), 116 (10), (100), 89 (6), 75 (6) 9, 145.3, 135.9, 134.5, 132.0, 131.8, 131.3, 129.5, 129.2, 129.1, 127.8, 127.6, 127.5, 127.4, 126.7 1, 141.6, 136.0, 135.0, 132.0, 131.7, 130.7, 130.5, 127.8, 124.6, 117.6, 60.5, 14 6,135.9,135.2,133.7,132.1,131.7,130.7,128.0,118.6,(EI) m/z 317 (M + ,14), 218 (8), 143 (12), 142 (100), 140 (6), 116 (9), 115 (87), 89 (6), 75 (7). CH 3 CN).…”

Section: Table 2 Use Of Visible-led Lights In the Intramolecular Phomentioning

confidence: 99%

“…6, 134.1, 133.2, 132.4, 131.8, 131.1, 128.4, 125.5, 125.4, 121.4, 121.1, 119.8, 20.6. GC-MS , 9), 245 (M + , 69), 181 21, 180 (100), 178 9, 153 6, 152 17, 151 7, 127 5, 90 9, 89 5, 77 11, 76 7, 75 5, 63 6, 51 (5). HRMS (TOF, ESI + ): calcd for C 13 H 11 NNaO 2 S (M+Na) + : 268.0403; Found: 268.0400.…”

Section: Isolation and Identification Of Productsmentioning

confidence: 99%

“…HRMS (TOF, ESI + ): calcd for C 16 H 11 NNaO 2 S (M+Na) + : 304.0403; Found: 304.0392. [5,6] [1,2]thiazino [3,4-c] 143.8, 143.7, 136.9, 132.4, 130.6, 130.5, 129.9, 129.2, 128.9, 128.8, 128.6, 125.3, 124.2, 123.4, 121.7 e] [1,2]thiazine 5,5-dioxide (6o). The product was purified by column chromatography on silica gel eluting with pentane/ EtOAc (100:0 → 70:30 %).…”

Section: -Methoxymentioning

confidence: 99%

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Synthesis of Dibenzosultams by “Transition-Metal-Free” Photoinduced Intramolecular Arylation of N-Aryl-2-halobenzenesulfonamides

et al. 2016

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A new and general synthetic route to prepare dibenzosultams is here reported. This approach involves the synthesis of N-aryl-2-halobenzenesulfonamides (3), followed by intramolecular C-C photoinduced arylation under soft conditions without the use of "Transition Metal". The photostimulated reactions exhibit very good tolerance to different substituent groups with good to excellent isolated yields (42-98%) of products. Moreover, it is shown that LED (λ = 395 nm) is an efficient light energy source to initiate efficiently the reactions. Theoretical inspection of the mechanism was made to probe the involvement of the radical-anion SRN1 process.

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Development of Synthetic Approaches to Biaryl Sultams via CH Functionalization

Gupta¹,

Laha²

2022

Handbook of CH-Functionalization

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Biaryl sultams represent a privileged molecular scaffold in drug discovery owing to their potential as a clinical candidate. Various developments toward the synthesis of diverse biaryl sultams including metal‐catalyzed and metal‐free CH functionalization involving CC/CN bond formation or annulative cyclization have been advanced in recent time. However, a transition metal‐catalyzed direct CH functionalization approach remains a powerful variant and has been utilized tremendously for the past several decades. The postsynthetic transformations of biaryl sultams to drug‐like molecules offer a tremendous possibility in drug discovery. In this article, we aim to provide an overview of various developments made in the synthetic approaches to biaryl sultams via CH functionalization, with a futuristic emphasis on their postsynthetic utility in accessing (hetero)biaryls containing an ortho ‐sulfonamide or amine functionality, a promising and potentially useful molecular scaffold in therapeutic discovery. The current challenges and a future perspective are also discussed briefly.

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Identification of N-(quinolin-8-yl)benzenesulfonamides as agents capable of down-regulating NFκB activity within two separate high-throughput screens of NFκB activation

Cited by 19 publications

References 23 publications

α–Intercalated cells defend the urinary system from bacterial infection

α–Intercalated cells defend the urinary system from bacterial infection

Synthesis of Dibenzosultams by “Transition-Metal-Free” Photoinduced Intramolecular Arylation of N-Aryl-2-halobenzenesulfonamides

Development of Synthetic Approaches to Biaryl Sultams via CH Functionalization

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