Synthesis and Anti‐Inflammatory Activity of 2‐Amino‐4,5,6,7‐tetrahydrobenzo[<i>b</i>]thiophene‐Derived NRF2 Activators

Mak, Kit‐Kay; Zhang, Shiming; Epemolu, Ola; Dinkova‐Kostova, Albena T.; Wells, Geoff; Gazaryan, I. G.; Sakirolla, Raghavendra; Zulkefeli, Mohd; Pichika, Mallikarjuna Rao

doi:10.1002/open.202200181

Cited by 6 publications

(1 citation statement)

References 46 publications

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“…As reported in the literature, Nrf2 protein level correlated with eGFR (17), proteinuria (18), diabetes mellitus (19), C-reactive protein (CRP) (20), and SLEDAI score (21) in renal diseases. In the present study in patients with LN, Nrf2 protein level positively correlated with eGFR and the SLEDAI score.…”

Section: Bivariate Correlation Analysis For Nrf2mentioning

confidence: 61%

Association of serum Nrf2 protein levels with disease activity and renal impairment in lupus nephritis

Li,

Guo,

Wei

et al. 2024

Front. Immunol.

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IntroductionWe aimed to investigate the relationship between nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression levels, lupus nephritis (LN) disease activity, and the degree of renal injury (based on the estimated glomerular filtration rate [eGFR]) in patients with LN.MethodsWe selected 40 healthy control participants and 102 patients with LN who were treated in the Second Hospital of Jilin University, China, for inclusion in this study. Patients with LN were classified into LN with high-eGFR and LN with low-eGFR groups. Nrf2 protein levels were measured in the serum and renal tissues of the participants in both groups to assess the correlation between Nrf2 protein levels and different LN disease states.ResultsThere was a significantly positive correlation between serum Nrf2 protein levels, the degree of renal injury, and systemic lupus erythematosus disease activity index (SLEDAI) scores in patients with LN. Nrf2 protein levels were higher in the LN with high-eGFR group than in the healthy control and LN with low-eGFR groups. In follow-up patients in the LN high eGFR group, Nrf2 protein levels decreased significantly after remission of disease activity.ConclusionNrf2 protein expression has a dual role in patients with LN. Nrf2 protein levels not only correlate with disease activity in patients with LN, but also with the degree of kidney injury. Before implementing targeted therapy for Nrf2, evaluating both Nrf2 protein expression and the disease state in patients with LN is necessary to better identify and place each patient in an appropriate patient group.

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Section: Bivariate Correlation Analysis For Nrf2mentioning

confidence: 61%

Association of serum Nrf2 protein levels with disease activity and renal impairment in lupus nephritis

Li,

Guo,

Wei

et al. 2024

Front. Immunol.

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Pharmacophore‐based, rationale design, and efficient synthesis of novel tetrahydrobenzo[b]thiophene candidates as potential dual Topo I/II inhibitors and DNA intercalators

Nofal,

Al‐Karmalawy,

Elmaaty

et al. 2024

Archiv der Pharmazie

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A series of tetrahydrobenzo[b]thiophene derivatives was designed and synthesized as dual topoisomerase (Topo) I/II inhibitors implicating potential DNA intercalation. Ethyl‐2‐amino‐3‐cyano‐4,5,6,7‐tetrahydrobenzo[b]thiophene‐4‐carboxylate (1) was prepared by modification of the Gewald reaction procedure using a Fe2O3 nanocatalyst and then it was used as a building block for the synthesis of tetrahydrobenzo[b]thiophene candidates (2–14). Interestingly, compound 14 showed the best cytotoxic potential against hepatocellular, colorectal, and breast cancer cell lines (IC50 = 7.79, 8.10, and 3.53 µM), respectively, surpassing doxorubicin at breast cancer (IC50 = 4.17 µM). Meanwhile, the Topo I and II inhibition assay displayed that compound 3 could exhibit the best inhibitory potential among the investigated candidates (IC50 = 25.26 and 10.01 nM), respectively, in comparison to camptothecin (IC50 = 28.34 nM) and doxorubicin (IC50 = 11.01 nM), as reference standards. In addition, the DNA intercalation assay showed that compound 14 could display the best binding affinity with an IC50 value of 77.82 µM in comparison to doxorubicin (IC50 = 58.03 µM). Furthermore, cell cycle and apoptosis analyses described that compound 3 prompts the G1 phase arrest in michigan cancer foundation‐7 cancer cells and increases the apoptosis ratio by 29.31% with respect to untreated cells (2.25%). Additionally, the conducted molecular docking assured the promising binding of the investigated members toward Topo I and II with potential DNA intercalation. Accordingly, the synthesized compounds could be treated as promising anticancer candidates for future optimization.

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Research progress on the role and inhibitors of Keap1 signaling pathway in inflammation

Ding,

Wu,

Zhan

et al. 2024

International Immunopharmacology

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Synthesis and Anti‐Inflammatory Activity of 2‐Amino‐4,5,6,7‐tetrahydrobenzo[b]thiophene‐Derived NRF2 Activators

Cited by 6 publications

References 46 publications

Association of serum Nrf2 protein levels with disease activity and renal impairment in lupus nephritis

Association of serum Nrf2 protein levels with disease activity and renal impairment in lupus nephritis

Pharmacophore‐based, rationale design, and efficient synthesis of novel tetrahydrobenzo[b]thiophene candidates as potential dual Topo I/II inhibitors and DNA intercalators

Research progress on the role and inhibitors of Keap1 signaling pathway in inflammation

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