From hit to lead: Structure-based discovery of naphthalene-1-sulfonamide derivatives as potent and selective inhibitors of fatty acid binding protein 4

Gao, Dingding; Dou, Hui-Xia; Su, Haixia; Zhang, Mingming; Wang, Ting; Liu, Qiu-Feng; Cai, Haiyan; Ding, Hong; Yang, Zhuo; Zhu, Weiliang; Xu, Yechun; Wang, He-Yao; Li, Yingxia

doi:10.1016/j.ejmech.2018.05.007

Cited by 21 publications

(16 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Then, commercially available β-alanine 10 was converted to corresponding methyl ester hydrochloride 11 , which was protected using fluorenylmethyloxycarbonyl chloride (Fmoc-Cl) to provide 12 . Hydrazinolysis of 12 led to the Fmoc-protected hydrazide 13 (Scheme ).…”

Section: Resultsmentioning

confidence: 99%

“…The β-aminoaldehyde 9 was obtained from 7 through borane-mediated reduction and subsequent oxidation of the resulting alcohol under Parikh−Doering conditions. Then, commercially available β-alanine 10 was converted to corresponding methyl ester hydrochloride 11, 50 which was protected using fluorenylmethyloxycarbonyl chloride (Fmoc-Cl) to provide 12. 51 Hydrazinolysis of 12 led to the Fmocprotected hydrazide 13 (Scheme 2).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Structure-Based Design and Development of Chemical Probes Targeting Putative MOR-CCR5 Heterodimers to Inhibit Opioid Exacerbated HIV-1 Infectivity

et al. 2021

View full text Add to dashboard Cite

Crystal structures of ligand-bound G-protein-coupled receptors provide tangible templates for rationally designing molecular probes. Herein, we report the structure-based design, chemical synthesis, and biological investigations of bivalent ligands targeting putative mu opioid receptor C−C motif chemokine ligand 5 (MOR-CCR5) heterodimers. The bivalent ligand VZMC013 possessed nanomolar level binding affinities for both the MOR and CCR5, inhibited CCL5-stimulated calcium mobilization, and remarkably improved anti-HIV-1 BaL activity over previously reported bivalent ligands. VZMC013 inhibited viral infection in TZM-bl cells coexpressing CCR5 and MOR to a greater degree than cells expressing CCR5 alone. Furthermore, VZMC013 blocked human immunodeficiency virus (HIV)-1 entry in peripheral blood mononuclear cells (PBMC) cells in a concentrationdependent manner and inhibited opioid-accelerated HIV-1 entry more effectively in phytohemagglutinin-stimulated PBMC cells than in the absence of opioids. A three-dimensional molecular model of VZMC013 binding to the MOR-CCR5 heterodimer complex is constructed to elucidate its mechanism of action. VZMC013 is a potent chemical probe targeting MOR-CCR5 heterodimers and may serve as a pharmacological agent to inhibit opioid-exacerbated HIV-1 entry.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: ■ Results and Discussionmentioning

confidence: 99%

Structure-Based Design and Development of Chemical Probes Targeting Putative MOR-CCR5 Heterodimers to Inhibit Opioid Exacerbated HIV-1 Infectivity

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The blots were detected by chemiluminescence detection regents (Thermo Fisher Scientific, Waltham, MA, USA). The protein levels were quantitated by densitometry analysis using Gel‐Pro‐Analyzer software 35 . The relative density ratio of FABP4 or PPAR‐γ was adjusted to β‐Actin and normalized to Vehicle group, Vehicle (+FFA) group or Vehicle (+PMA) group.…”

Section: Methodsmentioning

confidence: 99%

Combined treatment with FABP4 inhibitor ameliorates rosiglitazone‐induced liver steatosis in obese diabetic db/db mice

Chen

Huang

Gao

et al. 2021

Basic Clin Pharma Tox

View full text Add to dashboard Cite

Rosiglitazone has been reported to exert dual effects on liver steatosis, and it could exacerbate liver steatosis in obese animal models, which was suggested to be closely related to the elevated hepatic expression of FABP4. This study aimed to investigate whether combined treatment with FABP4 inhibitor I‐9 could alleviate rosiglitazone‐induced liver steatosis in obese diabetic db/db mice. Male C57BL/KsJ‐db/db mice were orally treated with rosiglitazone, rosiglitazone combined with I‐9 daily for 8 weeks. The liver steatosis was evaluated by triglyceride content and H&E staining. The expression of hepatic lipogenic genes or proteins in liver tissue or in FFA‐treated hepatocytes and PMA‐stimulated macrophages were determined by real‐time quantitative polymerase chain reaction (RT‐qPCR) or western blotting. Results showed that combined treatment with I‐9 decreased rosiglitazone‐induced increase in serum FABP4 level and expression of lipogenic genes in liver, especially FABP4, and ameliorated liver steatosis in db/db mice. Rosiglitazone‐induced intracellular TG accumulation and increased expression of FABP4 in the cultured hepatocytes and macrophages were also suppressed by combined treatment. We concluded that combined treatment with FABP4 inhibitor I‐9 could ameliorate rosiglitazone‐exacerbated elevated serum FABP4 level and ectopic liver fat accumulation in obese diabetic db/db mice without affecting its anti‐diabetic efficacy.

show abstract

“…Sulfonamide analogues have been used for many years for the drug development of novel lead candidates that treat various diseases and conditions. According to literature, these scaffolds have offered a wide range of pharmacological effects, such as antimicrobial, anti‐inflammatory, anti‐proliferative, anti‐parasitic, anti‐diabetic, and neuroprotective effects (Pan et al, 2013; Ceruso et al, 2015; Abbas et al, 2017; Li et al, 2018; Markowicz‐piasecka et al, 2018; Naaz et al, 2018; Peixoto & Beverly, 1987; Gao et al, 2018; Alafeefy et al, 2015; Scarim et al, 2019; Chohan et al, 2014; Peres et al, 2018; Rashad et al, 2014; Vieira et al, 2014; Badgujar et al, 2017; Brand et al, 2014; Dikhit et al, 2016; Kang et al, 2019; Katinas et al, 2017; Kachaeva et al, 2018; Vanga et al, 2018; El‐karim et al, 2018; Nakahata et al, 2018; Hackler et al, 2017; Galiana‐Roselló et al, 2013; Barbuceanu et al, 2014; Mishra et al, 2018; Ugwu et al, 2018; Abbasi et al, 2018). The simple structures of sulfonamide derivatives facilitate the design of their analogues and enable extensive biological activities.…”

Section: Sulfonamide‐based Conjugatesmentioning

confidence: 99%

An overview of sulfonamide‐based conjugates: Recent advances for tuberculosis treatment

Scarim

Pavan

2022

Drug Development Research

View full text Add to dashboard Cite

In 2019, tuberculosis (TB) caused approximately 1.4 million deaths around the world.TB is an infectious respiratory disease mainly caused by Mycobacterium tuberculosis.The lack of new drugs to treat drug-resistant strains is a principal factor for the continuous slow rise in TB infections. Sulfonamides are active moieties in various drugs used against several sicknesses, including TB. Our aim is to aid the development of new TB treatments and drugs by describing recent improvements (2011-2021) to sulfonamide-based compounds.

show abstract

From hit to lead: Structure-based discovery of naphthalene-1-sulfonamide derivatives as potent and selective inhibitors of fatty acid binding protein 4

Cited by 21 publications

References 45 publications

Structure-Based Design and Development of Chemical Probes Targeting Putative MOR-CCR5 Heterodimers to Inhibit Opioid Exacerbated HIV-1 Infectivity

Structure-Based Design and Development of Chemical Probes Targeting Putative MOR-CCR5 Heterodimers to Inhibit Opioid Exacerbated HIV-1 Infectivity

Combined treatment with FABP4 inhibitor ameliorates rosiglitazone‐induced liver steatosis in obese diabetic db/db mice

An overview of sulfonamide‐based conjugates: Recent advances for tuberculosis treatment

Contact Info

Product

Resources

About