Benzimidazole derivative M084 extends the lifespan of Caenorhabditis elegans in a DAF-16/FOXO-dependent way

被引：0
作者：
Ai-Jun Ding
Gui-Sheng Wu
Bin Tang
Xuechuan Hong
Michael X. Zhu
Huai-Rong Luo
机构：
[1] Chinese Academy of Sciences,State Key Laboratory of Phytochemistry and Plant Resources in West China, Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany
[2] University of Chinese Academy of Sciences,School of Pharmacy
[3] Southwest Medical University,Key Laboratory of Combinatorial Biosynthesis and Drug Discovery
[4] Wuhan University School of Pharmaceutical Sciences,Department of Integrative Biology and Pharmacology
[5] University of Texas Health Science Center at Houston,undefined
来源：
Molecular and Cellular Biochemistry | 2017年 / 426卷
关键词：
Aging; Benzimidazole derivative M084; Lifespan;
D O I：
暂无
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学科分类号：
摘要：
With the growth of aging population, there is increasing demand to develop strategy to improve the aging process and aging-related diseases. Benzimidazole and its derivatives are crucial heterocyclic backbone of many drugs and compounds with diverse therapeutic applications, including alleviation of aging-related diseases. Here, we investigate if the benzimidazole derivative n-butyl-[1H]-benzimidazol-2-amine (M084), a novel inhibitor of TRPC4 and TRPC5 channels and antidepressant, could affect the lifespan of Caenorhabditis elegans (C. elegans). Our results showed that M084 could extend the lifespan of C. elegans, delay age-related decline of phenotypes, and improve stress resistance. M084 could not extend the lifespan of the loss-of-function mutants of daf-16, daf-2, pdk-1, aak-2, clk-1, isp-1, sir-2.1, and skn-1. M084 could decrease the ATP level and increase the gene expression of mitochondrial unfolded protein response factors. Thus, M084 might inhibit the mitochondrial respiration, activate mitochondrial unfolded protein response and AMPK, recruite SIR-2.1 and SKN-1, and finally through the transcription factor DAF-16, delay the aging process of C. elegans. Our findings reveal the new pharmaceutical potential of benzimidazole derivatives and provide clue for developing novel anti-aging agents.
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页码：101 / 109
页数：8
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  • [1] Briguglio I(2015)Benzotriazole: an overview on its versatile biological behavior Eur J Med Chem 97 612-648
  • [2] Piras S(2010)Interaction of anthelmintic drugs with P-glycoprotein in recombinant LLC-PK1-mdr1a cells Chem Biol Interact 186 280-286
  • [3] Corona P(2016)Association between proton pump inhibitors and microscopic colitis: implications for practice and future research Ann Pharmacother 74 846-850
  • [4] Gavini E(2016)P21 (Cdc42/Rac)-activated kinase 1 (pak1) is associated with cardiotoxicity induced by antihistamines Arch Pharm Res 29 893-900
  • [5] Nieddu M(1985)Liquid chromatographic analysis of enviradene, a new antiviral agent, in plasma and its application in bioavailability studies in the dog J Pharm Sci 29 126-137
  • [6] Boatto G(2014)Validated spectrofluorimetric determination of two pharmaceutical antihypertensive mixtures containing amlodipine besylate together with either candesartan cilexetil or telmisartan Luminescence 24 3680-3686
  • [7] Carta A(2015)Benzimidazole-based silver(I)- Appl Organomet Chem 95 500-513
  • [8] Dupuy J(2016)-heterocyclic carbene complexes as anti-bacterials: synthesis, crystal structures and nucleic acids interaction studies Bioorg Med Chem 8 1953-1967
  • [9] Alvinerie M(2015)Synthesis and investigation of novel benzimidazole derivatives as antifungal agents Eur J Med Chem 4 368-375
  • [10] Menez C(2016)Development of benzimidazole derivatives to inhibit HIV-1 replication through protecting APOBEC3G protein Future Med Chem 69 53-62
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