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Synthesis and Biological Evaluation of Novel Benzimidazole Derivatives and Analogs Targeting the NLRP3 Inflammasome.

ABSTRACT: A series of benzo[d]imidazole analogues of thiabenzole were synthesized and their antiinflammatory activities toward NLRP3 (nucleotide-binding domain leucine-rich repeat containing protein family?pyrin domain-containing 3?also known as cryopyrin or NALP3) inflammasome were evaluated in vitro. Two lead compounds, TBZ-09 and TBZ-21, were identified by antiproduction of IL-1?. In the second round of biological evaluation, based on the lead, 34 more compounds were synthesized and their in vitro anti-inflammatory activities were investigated. Several compounds were identified as anti-inflammatory agents that can reduce IL-1? expression in a dosedependent manner. A preliminary structure-activity relationship is also summarized here.

SUBMITTER: Pan L

PROVIDER: S-EPMC6155809 | biostudies-other | 2017 Jan

REPOSITORIES: biostudies-other

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Synthesis and Biological Evaluation of Novel Benzimidazole Derivatives and Analogs Targeting the NLRP3 Inflammasome.

Pan Liangkun L Hang Nan N Zhang Chao C Chen Yu Y Li Shuchun S Sun Yang Y Li Zhongjun Z Meng Xiangbao X

Molecules (Basel, Switzerland) 20170130 2

A series of benzo[d]imidazole analogues of thiabenzole were synthesized and their antiinflammatory activities toward NLRP3 (nucleotide-binding domain leucine-rich repeat containing protein family，pyrin domain-containing 3，also known as cryopyrin or NALP3) inflammasome were evaluated in vitro. Two lead compounds, TBZ-09 and TBZ-21, were identified by antiproduction of IL-1β. In the second round of biological evaluation, based on the lead, 34 more compounds were synthesized and their in vitro anti ...[more]

PMID: 28146092

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