Synthesis and characterization of styryl-BODIPY derivatives for monitoring in vitro Tau aggregation

• Published in: Sensors and actuators. B, Chemical Vol. 244; pp. 673 - 683
• Main Authors: Mani, Vedamalai, Krishnakumar, V. Guru, Gupta, Sharad, Mori, Shigeki, Gupta, Iti
• Format: Journal Article
• Language: English
• Published: Lausanne Elsevier B.V 01-06-2017; Elsevier Science Ltd
• Subjects: Agglomeration; Atomic force microscopy; BODIPY; Cell culture; Chemical synthesis; Corrosion inhibitors; Derivatives; Dyes; Emissions; Fluorescence; Methane; Proteins; Tau; Wolff-Kishner reduction; Fluorescence; Tau; BODIPY; Wolff-Kishner reduction
• ISSN: 0925-4005; 1873-3077
• DOI: 10.1016/j.snb.2016.12.104

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•A new method for the synthesis of α-BODIPY is reported.•The as-synthesized α-BODIPY has been used to synthesize biologically important styryl-BODIPY derivatives.•Quinoxaline appended BODIPY derivative is successfully used to monitor the tau aggregation.•The probe exhibits good cell membrane permeability and 95% cell viability in HeLa cells.
New synthetic strategy to synthesize α-methyl BODIPY derivatives from dipyrromethanes is reported. The method involves regioselective formylation of dipyrromethane followed by modified Wolff-Kishner reduction. The photophysical, electrochemical and computational studies of α-methyl BODIPY derivatives have been investigated in detail. The α-methyl BODIPY derivative was utilized further to prepare biologically important functionalized styryl-BODIPY library in high yield using microwave assisted Knoevenagel condensation. These synthesized dye derivatives were screened to find a potential candidate to track real-time in vitro tau protein fibrillization. Quinoxaline functionalized styryl-BODIPY derivative (5i) exhibited significant fluorescence enhancement upon binding to tau fibrils. Furthermore, tau-5i conjugate was systematically characterized by emission, aggregation kinetics, fluorescence microscopy and Atomic Force Microscopy techniques. Cell culture studies proved that compound 5i was cell permeable and non-toxic to live cells. In addition, a mechanism by which 5i interacts with tau fibrils has been elucidated which can be potentially exploited to further develop reporting dyes and inhibitors for tau aggregates.