title: Thiosemicarbazone modification of 3-acetyl coumarin inhibits Aβ peptide aggregation and protect against Aβ-induced cytotoxicity.
abstract: Aggregation of amyloid β peptide (Aβ) is an important event in the progression of Alzheimer's disease. Therefore, among the available therapeutic approaches to fight with disease, inhibition of Aβ aggregation is widely studied and one of the promising approach for the development of treatments for Alzheimer's disease. Thiosemicarbazone compounds are known for their variety of biological activities. However, the potential of thiosemicarbazone compounds towards inhibition of Aβ peptide aggregation and the subsequent toxicity is little explored. Herein, we report synthesis and x-ray crystal structure of novel compound 3-acetyl coumarin thiosemicarbazone and its efficacy toward inhibition of Aβ(1-42) peptide aggregation. Our results indicate that 3-acetyl coumarin thiosemicarbazone inhibits Aβ(1-42) peptide aggregation up to 80% compared to the parent 3-acetyl coumarin which inhibits 52%. Further, 3-acetyl coumarin thiosemicarbazone provides neuroprotection against Aβ-induced cytotoxicity in SH-SY5Y cell line. These findings indicate that thiosemicarbazone modification renders 3-acetyl coumarin neuroprotective properties.
authors.affiliation: Bioprospecting Group, Agharkar Research Institute, G. G. Agarkar Road, Pune, 411004, India.
authors.forename: Dnyanesh S
authors.initials: DS
authors.lastname: Ranade
authors.affiliation: Bioprospecting Group, Agharkar Research Institute, G. G. Agarkar Road, Pune, 411004, India. Electronic address: ambapat@gmail.com.
authors.forename: Archika M
authors.initials: AM
authors.lastname: Bapat
authors.affiliation: Bioprospecting Group, Agharkar Research Institute, G. G. Agarkar Road, Pune, 411004, India.
authors.forename: Shefali N
authors.initials: SN
authors.lastname: Ramteke
authors.affiliation: Bioprospecting Group, Agharkar Research Institute, G. G. Agarkar Road, Pune, 411004, India.
authors.forename: Bimba N
authors.initials: BN
authors.lastname: Joshi
authors.affiliation: Unité de Catalyse et Chimie du Solide, UMR CNRS 8012, École Nationale Supérieure de, Chimie de Lille, BP, 90108-59652, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Roussel
authors.affiliation: Laboratoire de Cristallographie et RMN Biologiques, UMR CNRS 8015, Université Paris Descartes, 75270, Paris Cedex 06, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Tomas
authors.affiliation: Laboratoire de Cristallographie et RMN Biologiques, UMR CNRS 8015, Université Paris Descartes, 75270, Paris Cedex 06, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Deschamps
authors.affiliation: Bioprospecting Group, Agharkar Research Institute, G. G. Agarkar Road, Pune, 411004, India. Electronic address: kulkarniari@gmail.com.
authors.forename: Prasad P
authors.initials: PP
authors.lastname: Kulkarni
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000633:toxicity*; D045744:Cell Line, Tumor; D003374:Coumarins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology; D010446:Peptide Fragments / Q000737:chemistry* / Q000633:toxicity*; D066329:Protein Aggregates / Q000187:drug effects*; D013882:Thiosemicarbazones / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D003374:Coumarins; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D066329:Protein Aggregates; D013882:Thiosemicarbazones; C075222:amyloid beta-protein (1-42)
keywords: Aggregation; Alzheimer's disease; Amyloid beta peptide; Cytotoxicity; Fluorescence; Thiosemicarbazone