Synthesis and anti-endoplasmic reticulum stress activity of N-substituted-2-arylcarbonylhydrazinecarbothioamides

Choi, Hyun-Woo; Yun, Wheesahng; Lee, Jung-Hun; Jang, Seoul; Park, Sang Won; Kim, Dong Hwan; Seon, Kyoung Pyo; Hyun, Jung-mi; Jeong, Kwiwan; Ku, Jin‐Mo; Nam, Tae‐gyu

doi:10.1007/s00044-019-02442-1

Cited by 15 publications

(7 citation statements)

References 17 publications

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“…Anti-ER stress activity of the compounds, expressed as IC 50 , was evaluated using our cell-based reporter assay based on multiplex renilla luciferase activity driven by GRP78 gene. Cytotoxicity was also measured using the luciferase assay as described in Methods section, 15 , 16 expressed as CC 50 and displayed in Table 1 along with IC 50 .…”

Section: Resultsmentioning

confidence: 99%

“…Cytotoxicity was also measured using the luciferase assay as described in Methods section, 15 , 16 expressed as CC 50 and displayed in Table 1 along with IC 50 .…”

Section: Resultsmentioning

confidence: 99%

“…The stable human embryonic kidney (HEK 293) cell line harboring a reporter gene expressed by human grp78 promoter was used as previously described. 15 Synthesized human grp78 promoter (−137~+25) containing three ER stress response elements (ERSE) in tandem was cloned into pGL4.79 vector (Promega, Madison, USA). A stable human embryonic kidney (HEK 293) cell line harboring the reporter gene was selected under 400 μg/mL of G418 selection pressure.…”

Section: Methodsmentioning

confidence: 99%

“…13 In search of novel chemical chaperones, we have reported that hydroxynaphthoic acids (HNAs) showed about an order of magnitude lower EC 50 than known chemical chaperones such as salicylic acid 14 and t--UDCA. 15 HNAs were identified through a cell-based assay we have developed and decreased ER stress markers including GRP78 and phosphorylated PERK. 14,16 Especially, 3-Hydroxy-2-naththoic acid (3-HNA) showed excellent anti-diabetic effects including recovery of insulin sensitivity and glucose-lowering activity in ob/ob mouse when administered orally through ER stress-reducing activity.…”

Section: Introductionmentioning

confidence: 99%

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Bi-aryl Analogues of Salicylic Acids: Design, Synthesis and SAR Study to Ameliorate Endoplasmic Reticulum Stress

Kim¹,

Kim²,

Choi³

et al. 2021

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Introduction Endoplasmic reticulum (ER) stress condition is characterized as the accumulation of misfolded or unfolded proteins in lumen of ER. This condition has been implicated in various diseases and pathologies including β-cell apoptosis, Alzheimer’s disease and atherosclerosis. We have reported that hydroxynaphthoic acids (HNA), naphthalene analogues of salicylic acid (SA), reduced ER stress. In this study, we explored structural modification to bi-aryl analogues of SA. Methods Palladium-catalyzed cross-coupling was applied to synthesize bi-aryl analogues of SA. Anti-ER stress activity was monitored by using our cell-based assay system where ER stress is induced by tunicamycin. To monitor ER stress markers, ER stress was induced physiologically relevant palmitate system. Results Many analogues decreased ER stress signal induced by tunicamycin. Compounds creating dihedral angle between Ar group and SA moiety generally increased the activity but gave some cytotoxicity to indicate the crucial role of flat conformation of aromatic region. The best compound (16e) showed up to almost 6-fold and 90-fold better activity than 3-HNA and tauro-ursodeoxycholic acid, positive controls, respectively. ER stress markers such as p-PERK and p-JNK were accordingly decreased in Western blotting upon treatment of 16e under palmitate-induced condition. Conclusion Anti-ER stress activity and toxicity profile of bi-aryl analogues of SA could provide a novel platform for potential therapy for protein misfolding diseases.

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Section: Resultsmentioning

confidence: 99%

“…Cytotoxicity was also measured using the luciferase assay as described in Methods section, 15 , 16 expressed as CC 50 and displayed in Table 1 along with IC 50 .…”

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bi-aryl Analogues of Salicylic Acids: Design, Synthesis and SAR Study to Ameliorate Endoplasmic Reticulum Stress

Kim¹,

Kim²,

Choi³

et al. 2021

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“…Compounds B1–B12 were obtained in our laboratory and described in the publication [ 26 , 27 , 28 , 29 , 30 , 31 ].…”

Section: Methodsmentioning

confidence: 99%

New Application of 1,2,4-Triazole Derivatives as Antitubercular Agents. Structure, In Vitro Screening and Docking Studies

et al. 2020

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A series of 1,2,4-triazole derivatives were synthesized and assigned as potential anti-tuberculosis substances. The molecular and crystal structures for the model compounds C1, C12, and C13 were determined using X-ray analysis. The X-ray investigation confirmed the synthesis pathway and the assumed molecular structures for analyzed 1,2,4-triazol-5-thione derivatives. The conformational preferences resulting from rotational degrees of freedom of the 1,2,4-triazole ring substituents were characterized. The lipophilicity (logP) and electronic parameters as the energy of frontier orbitals, dipole moments, NBO net charge distribution on the atoms, and electrostatic potential distribution for all structures were calculated at AM1 and DFT/B3LYP/6-311++G(d,p) level. The in vitro test was done against M. tuberculosis H37Ra, M. phlei, M. smegmatis, and M. timereck. The obtained results clearly confirmed the antituberculosis potential of compound C4, which turned out to be the most active against Mycobacterium H37Ra (MIC = 0.976 μg/mL), Mycobaterium pheli (MIC = 7.81 μg/mL) and Mycobacerium timereck (62.6 μg/mL). Satisfactory results were obtained with compounds C8, C11, C14 versus Myc. H37Ra, Myc. pheli, Myc. timereck (MIC = 31.25−62.5 μg/mL). The molecular docking studies were carried out for all investigated compounds using the Mycobacterium tuberculosis cytochrome P450 CYP121 enzyme as molecular a target connected with antimycobacterial activity.

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Synthesis, Characterizations, Crystal Structure, DFT, and Hirshfeld Surface Analysis of 4-Cyclohexyl-1-(thiophene-2-carbonyl)thiosemicarbazide

et al. 2022

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Synthesis and anti-endoplasmic reticulum stress activity of N-substituted-2-arylcarbonylhydrazinecarbothioamides

Cited by 15 publications

References 17 publications

Bi-aryl Analogues of Salicylic Acids: Design, Synthesis and SAR Study to Ameliorate Endoplasmic Reticulum Stress

Bi-aryl Analogues of Salicylic Acids: Design, Synthesis and SAR Study to Ameliorate Endoplasmic Reticulum Stress

New Application of 1,2,4-Triazole Derivatives as Antitubercular Agents. Structure, In Vitro Screening and Docking Studies

Synthesis, Characterizations, Crystal Structure, DFT, and Hirshfeld Surface Analysis of 4-Cyclohexyl-1-(thiophene-2-carbonyl)thiosemicarbazide

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