Diphenyl triazine hybrids inhibit ?-synuclein fibrillogenesis: design, synthesis and in vitro efficacy studies

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dc.contributor.author Maqbool, Mudasir
dc.contributor.author Gadhavi, Joshna
dc.contributor.author Hivare, Pravin
dc.contributor.author Gupta, Sharad
dc.contributor.author Hoda, Nasimul
dc.date.accessioned 2020-11-05T06:07:18Z
dc.date.available 2020-11-05T06:07:18Z
dc.date.issued 2020-12
dc.identifier.citation Maqbool, Mudasir; Gadhavi, Joshna; Hivare, Pravin; Gupta, Sharad, Hoda, Nasimul, "Diphenyl triazine hybrids inhibit ?-synuclein fibrillogenesis: design, synthesis and in vitro efficacy studies", European Journal of Medicinal Chemistry, DOI: 10.1016/j.ejmech.2020.112705, vol. 207, Dec. 2020. en_US
dc.identifier.issn 0223-5234
dc.identifier.uri https://doi.org/10.1016/j.ejmech.2020.112705
dc.identifier.uri https://repository.iitgn.ac.in/handle/123456789/5841
dc.description.abstract Aggregation of ?-synuclein (?-syn) is one of the central hypotheses for Parkinson's disease (PD), therefore, its inhibition and disaggregation is an optimistic approach for the treatment of PD. Here, we report design, synthesis and in-vitro efficacy studies of a series of diphenyl triazine hybrids as potential inhibitors of ?-syn fibrillogenesis. From the docking studies, we concluded that compounds A1, A2, A4, A8 and A9 display promising binding affinity with the essential residues of ?-syn with binding energy values: ?6.0, ?7.0, ?6.3, ?6.6 and ?6.7 kcal/mol respectively. The target compounds were synthesized using multistep organic synthesis reactions. Compounds A1, A2 A4, A8 and A9 showed a significant lowering of the ?-syn fibril formation during Thioflavin-T assay and fluorescence microscopy. In addition, these compounds A1, A2, A4, A8 and A9 also proved to be good disaggregators in the pre-aggregated form of ?-syn. Most of the compounds exhibited no cytotoxicity in mouse embryonic fibroblast (MEF) and human adenocarcinomic alveolar basal epithelial cells (A549) except A2. Overall, diphenyl triazine-based compounds can be further investigated for the treatment of synucleinopathies and for Lewy body dementia in which ?-syn is predominantly observed.
dc.description.statementofresponsibility by Mudasir Maqbool, Joshna Gadhavi, Pravin Hivare, Sharad Gupta and Nasimul Hoda
dc.language.iso en_US en_US
dc.publisher Elsevier en_US
dc.subject Neurodegeneration en_US
dc.subject Parkinson's disease en_US
dc.subject Protein aggregation en_US
dc.subject Drug design en_US
dc.subject Synthesis en_US
dc.subject Diphenyltriazine en_US
dc.title Diphenyl triazine hybrids inhibit ?-synuclein fibrillogenesis: design, synthesis and in vitro efficacy studies en_US
dc.type Article en_US
dc.relation.journal European Journal of Medicinal Chemistry

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