Tags

Type your tag names separated by a space and hit enter

Marine derived xyloketal derivatives exhibit anti-stress and anti-ageing effects through HSF pathway in Caenorhabditis elegans.
Eur J Med Chem. 2018 Mar 25; 148:63-72.EJ

Abstract

Ageing is a complex but universal phenomenon that progressively challenges the homeostasis network and finally leads to the dysfunction of organisms and even death. Previous studies demonstrated that xyloketal B and its derivatives, a series of marine novel ketone compounds, possessed unique antioxidative effects on endothelial and neuronal oxidative injuries. In this study, we examined the effects of xyloketal derivatives on extending lifespan and healthspan of Caenorhabditis elegans. The results showed that most selected xyloketals could protect Caenorhabditis elegans against heat stress and extend the lifespan of worms. Compound 15, a benzo-1, 3-oxazine xyloketal derivative, possessed most potent effect in anti-heat stress assay and significantly attenuated ageing-related decrease of pumping and bending of the worms in healthspan assay. In addition, the beneficial effect of 15 was abolished in PS3551 worms, a strain that possesses non-functional heat shock transcription factor-1 (HSF-1). Furthermore, 15 increased the expression of heat shock protein 70 (HSP70), a downstream molecular chaperone of HSF-1. These results indicated that HSF-1 might contribute to the protective effect of this compound in Caenorhabditis elegans ageing. Molecular docking studies suggested that these xyloketal derivatives were bound to the DNA binding domain of HSF-1, promoted the conformation of HSF-1, thus strengthened the interaction between the HSF-1 and related DNA. ALA-67, ASN-74 and LYS-80 of binding region might be the key amino residues during the interaction. Finally, compound 15 could reduce the paralysis of the CL4176 worms, a transgenic strain expressing human Aβ3-42 under a temperature-inducible system. Collectively, these data indicate that xyloketals have potential implications for further evaluation in anti-ageing studies.

Authors+Show Affiliations

School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275, PR China.School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275, PR China.Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Disease, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510275, PR China.Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-evaluation of Post-marketed TCM, Guangdong Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, PR China.Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Disease, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510275, PR China. Electronic address: peizhong@mail.sysu.edu.cn.School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275, PR China. Electronic address: cespjy@mail.sysu.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29454917

Citation

Zhou, Jie-Bin, et al. "Marine Derived Xyloketal Derivatives Exhibit Anti-stress and Anti-ageing Effects Through HSF Pathway in Caenorhabditis Elegans." European Journal of Medicinal Chemistry, vol. 148, 2018, pp. 63-72.
Zhou JB, Zheng YL, Zeng YX, et al. Marine derived xyloketal derivatives exhibit anti-stress and anti-ageing effects through HSF pathway in Caenorhabditis elegans. Eur J Med Chem. 2018;148:63-72.
Zhou, J. B., Zheng, Y. L., Zeng, Y. X., Wang, J. W., Pei, Z., & Pang, J. Y. (2018). Marine derived xyloketal derivatives exhibit anti-stress and anti-ageing effects through HSF pathway in Caenorhabditis elegans. European Journal of Medicinal Chemistry, 148, 63-72. https://doi.org/10.1016/j.ejmech.2018.02.028
Zhou JB, et al. Marine Derived Xyloketal Derivatives Exhibit Anti-stress and Anti-ageing Effects Through HSF Pathway in Caenorhabditis Elegans. Eur J Med Chem. 2018 Mar 25;148:63-72. PubMed PMID: 29454917.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Marine derived xyloketal derivatives exhibit anti-stress and anti-ageing effects through HSF pathway in Caenorhabditis elegans. AU - Zhou,Jie-Bin, AU - Zheng,Ying-Lin, AU - Zeng,Yi-Xuan, AU - Wang,Jia-Wei, AU - Pei,Zhong, AU - Pang,Ji-Yan, Y1 - 2018/02/10/ PY - 2017/08/27/received PY - 2018/02/08/revised PY - 2018/02/09/accepted PY - 2018/2/20/pubmed PY - 2018/3/24/medline PY - 2018/2/19/entrez KW - Anti-ageing KW - Caenorhabditis elegans KW - Heat shock protein KW - Heat shock transcription factor-1 KW - Xyloketal SP - 63 EP - 72 JF - European journal of medicinal chemistry JO - Eur J Med Chem VL - 148 N2 - Ageing is a complex but universal phenomenon that progressively challenges the homeostasis network and finally leads to the dysfunction of organisms and even death. Previous studies demonstrated that xyloketal B and its derivatives, a series of marine novel ketone compounds, possessed unique antioxidative effects on endothelial and neuronal oxidative injuries. In this study, we examined the effects of xyloketal derivatives on extending lifespan and healthspan of Caenorhabditis elegans. The results showed that most selected xyloketals could protect Caenorhabditis elegans against heat stress and extend the lifespan of worms. Compound 15, a benzo-1, 3-oxazine xyloketal derivative, possessed most potent effect in anti-heat stress assay and significantly attenuated ageing-related decrease of pumping and bending of the worms in healthspan assay. In addition, the beneficial effect of 15 was abolished in PS3551 worms, a strain that possesses non-functional heat shock transcription factor-1 (HSF-1). Furthermore, 15 increased the expression of heat shock protein 70 (HSP70), a downstream molecular chaperone of HSF-1. These results indicated that HSF-1 might contribute to the protective effect of this compound in Caenorhabditis elegans ageing. Molecular docking studies suggested that these xyloketal derivatives were bound to the DNA binding domain of HSF-1, promoted the conformation of HSF-1, thus strengthened the interaction between the HSF-1 and related DNA. ALA-67, ASN-74 and LYS-80 of binding region might be the key amino residues during the interaction. Finally, compound 15 could reduce the paralysis of the CL4176 worms, a transgenic strain expressing human Aβ3-42 under a temperature-inducible system. Collectively, these data indicate that xyloketals have potential implications for further evaluation in anti-ageing studies. SN - 1768-3254 UR - https://www.unboundmedicine.com/medline/citation/29454917/Marine_derived_xyloketal_derivatives_exhibit_anti_stress_and_anti_ageing_effects_through_HSF_pathway_in_Caenorhabditis_elegans_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0223-5234(18)30158-2 DB - PRIME DP - Unbound Medicine ER -