title: Repositioning nordihydroguaiaretic acid as a potent inhibitor of systemic amyloidosis and associated cellular toxicity.
abstract: Although the cure of amyloid related neurodegenerative diseases, non-neuropathic amyloidogenic diseases and non-neuropathic systemic amyloidosis are appealing energetic research attempts, beneficial medication is still to be discovered. There is a need to explore intensely stable therapeutic compounds, potent enough to restrict, disrupt or wipe out such toxic aggregates. We had performed a comprehensive biophysical, computational and cell based assay, that shows Nordihydroguaiaretic acid (NA) not only significantly inhibits heat induced hen egg white lysozyme (HEWL) fibrillation but also disaggregates preformed HEWL fibrils and reduces the cytoxicity of amyloid fibrils as well as disaggregated fibrillar species. The inhibitory potency of NA was determined by an IC50of 26.3 μM. NA was also found to effectively inhibit human lysozyme (HL) fibrillation. NA interferes in the amyloid fibrillogenesis process by interacting hydrophobically with the amino acid residues found in highly prone amyloid fibril forming region of HEWL as explicated by molecular docking results. The results recommend NA as a probable neuroprotective and promising inhibitor for the therapeutic advancement prospective against amyloid related diseases.
authors: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India.
authors: Saima
authors: S
authors: Nusrat
authors: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India.
authors: Nida
authors: N
authors: Zaidi
authors: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India.
authors: Masihuz
authors: M
authors: Zaman
authors: National Centre for Cell Science, Pune 411007, India.
authors: Sehbanul
authors: S
authors: Islam
authors: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India.
authors: Mohammad Rehan
authors: MR
authors: Ajmal
authors: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India.
authors: Mohammad Khursheed
authors: MK
authors: Siddiqi
authors: National Centre for Cell Science, Pune 411007, India.
authors: Manas Kumar
authors: MK
authors: Santra
authors: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India. Electronic address: rizwanhkhan@hotmail.com.
authors: Rizwan Hasan
authors: RH
authors: Khan
mesh_terms: D000682:Amyloid / Q000737:chemistry; D000686:Amyloidosis / Q000188:drug therapy / Q000378:metabolism*; D052160:Benzothiazoles; D045744:Cell Line, Tumor; D006358:Hot Temperature; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D000075363:Immunoglobulin Light-chain Amyloidosis; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008027:Light; D009637:Masoprocol / Q000737:chemistry*; D008856:Microscopy, Fluorescence; D062105:Molecular Docking Simulation; D009113:Muramidase / Q000737:chemistry; D009391:Nephelometry and Turbidimetry; D066329:Protein Aggregates; D011485:Protein Binding; D011487:Protein Conformation; D012542:Scattering, Radiation; D013050:Spectrometry, Fluorescence; D013844:Thiazoles / Q000737:chemistry
chemical_list: D000682:Amyloid; D052160:Benzothiazoles; D066329:Protein Aggregates; D013844:Thiazoles; C009462:thioflavin T; D009637:Masoprocol; C421864:hen egg lysozyme; D009113:Muramidase
keywords: Amyloid fibrils; Cytotoxicity; Disaggregation; IC(50); Molecular docking