Chalcone: A potential scaffold for NLRP3 inflammasome inhibitors

Thapa, Pritam; Upadhyay, Sunil P.; Singh, Vikas; Boinpelly, Varun C; Zhou, Jianping; Johnson, David K.; Gurung, Prajwal; Lee, Eung Seok; Sharma, Ram; Sharma, Mukut

doi:10.1016/j.ejmcr.2022.100100

Cited by 11 publications

(7 citation statements)

References 169 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Chalcones are natural compounds with α, β unsaturated carbonyl group (Michael acceptor) found in many plants and have gained attention for their medicinal properties [213,214]. We and others investigated some chalcones for their potential as NLRP3 inhibitors [215,216]. Our preliminary data encourage further development of more potent NLRP3 inhibitors based on this chalcone scaffold which could lead to the development of novel treatments for epilepsy and other inflammatory diseases.…”

Section: Nlrp3 Inflammasome Inhibitors and Their Limitations As Remed...mentioning

confidence: 76%

NLRP3 Inflammasome Inhibitors for Antiepileptogenic Drug Discovery and Development

Haque,

Thapa,

Burns

et al. 2024

Preprint

View full text Add to dashboard Cite

Epilepsy is one of the most prevalent and serious brain disorders, affecting 70 million people worldwide. Antiseizure medications (ASMs) though relieve symptoms and prevent the occurrence of future seizures in epileptic patients have limited effect on epileptogenesis. Addressing the multifaceted nature of epileptogenesis and its association with Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated neuroinflammation requires a comprehensive understanding of the underlying mechanisms for development of targeted therapeutic strategies beyond conventional antiseizure treatments. Several types of NLRP3 inhibitors have been developed and their effect has been validated both in vitro and in vivo models of epileptogenesis. In this review, we discuss the advances in understanding the regulatory mechanisms of NLRP3 activation as well as progress made and challenges facing in the development of NLRP3 inhibitors for the treatment of epilepsy.

show abstract

Section: Nlrp3 Inflammasome Inhibitors and Their Limitations As Remed...mentioning

confidence: 76%

NLRP3 Inflammasome Inhibitors for Antiepileptogenic Drug Discovery and Development

Haque,

Thapa,

Burns

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Although currently there are no approved drugs targeting NLRP3 for clinical use, recent advanced studies have revealed the discovery of small molecule compounds targeting the NLRP3 in ammasome. Chalcone has been suggested as a potential scaffold for NLRP3 in ammasome inhibitors [40]. Several classes of compounds such as sulfonylureas, sulfonamides, avonoids, and α, β unsaturated carbon containing molecules, have also been explored as NLRP3 in ammasome inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Investigating the Therapeutic Effects of Novel Compounds Targeting Inflammasome and IL-1β and IL-6 Signaling Pathways in Spinocerebellar Ataxia Type 3

Chen

Chang

et al. 2023

Preprint

View full text Add to dashboard Cite

At least seven dominantly inherited spinocerebellar ataxias (SCA) are caused by expansions of polyglutamine (polyQ)-encoding CAG repeat. The misfolded and aggregated polyQ-expanded proteins increase reactive oxygen species (ROS), cellular toxicity and neuroinflammation in the disease pathogenesis. In this study, we evaluated the anti-inflammatory potentials of coumarin derivatives LM-021, LMDS-1 and LMDS-2, and pharmacological chaperone tafamidis that stabilizes the correctly folded tetrameric transthyretin protein, using mouse BV-2 microglia and SCA3 ATXN3/Q75-GFP SH-SY5Y cells. The four tested compounds displayed anti-inflammatory activity by suppressing NO, IL-1β, IL-6 and TNF-α production and CD68, MHCII expression in LPS/IFN-γ-stimulated BV-2 microglia. In retinoic acid-differentiated ATXN3/Q75-GFP-expressing SH-SY5Y cells inflamed with LPS/IFN-γ-primed BV-2 conditioned medium, treatment with test compounds mitigated the increased caspase 1 activity and lactate dehydrogenase release, reduced ROS and ATXN3/Q75 aggregation, and promoted neurite outgrowth. Examination of inflammasome, IL-1β and IL-6-mediated signaling pathways revealed that LM-021, LMDS-1, LMDS-2 and tafamidis decreased NLRP1, JNK/JUN, IκBα/P65, P38/STAT1 and/or JAK2/STAT3 signaling. The study results suggest the potential of LM-021, LMDS-1, LMDS-2 and tafamidis in treating SCA3 and probable other polyQ diseases.

show abstract

“…Chalcones are natural compounds with an α, β unsaturated carbonyl group (Michael acceptor) found in many plants and have gained attention for their medicinal properties [ 210 , 211 ]. We and others investigated some chalcones for their potential as NLRP3 inhibitors [ 212 , 213 ]. Our preliminary data encourage the further development of more potent NLRP3 inhibitors based on this chalcone scaffold, which could lead to the development of novel treatments for epilepsy and other inflammatory diseases.…”

Section: Nlrp3 Inflammasome In Epilepsymentioning

confidence: 99%

NLRP3 Inflammasome Inhibitors for Antiepileptogenic Drug Discovery and Development

Haque,

Thapa,

Burns

et al. 2024

IJMS

Self Cite

View full text Add to dashboard Cite

Epilepsy is one of the most prevalent and serious brain disorders and affects over 70 million people globally. Antiseizure medications (ASMs) relieve symptoms and prevent the occurrence of future seizures in epileptic patients but have a limited effect on epileptogenesis. Addressing the multifaceted nature of epileptogenesis and its association with the Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated neuroinflammation requires a comprehensive understanding of the underlying mechanisms of these medications for the development of targeted therapeutic strategies beyond conventional antiseizure treatments. Several types of NLRP3 inhibitors have been developed and their effect has been validated both in in vitro and in vivo models of epileptogenesis. In this review, we discuss the advances in understanding the regulatory mechanisms of NLRP3 activation as well as progress made, and challenges faced in the development of NLRP3 inhibitors for the treatment of epilepsy.

show abstract

Chalcone: A potential scaffold for NLRP3 inflammasome inhibitors

Cited by 11 publications

References 169 publications

NLRP3 Inflammasome Inhibitors for Antiepileptogenic Drug Discovery and Development

NLRP3 Inflammasome Inhibitors for Antiepileptogenic Drug Discovery and Development

Investigating the Therapeutic Effects of Novel Compounds Targeting Inflammasome and IL-1β and IL-6 Signaling Pathways in Spinocerebellar Ataxia Type 3

NLRP3 Inflammasome Inhibitors for Antiepileptogenic Drug Discovery and Development

Contact Info

Product

Resources

About