Exploring the Propensities of Fluorescent Carbazole Analogs toward the Inhibition of Amyloid Aggregation in Type 2 Diabetes: An Experimental and Theoretical Endeavor.

Amyloid aggregation is a pathological trait observed in many incurable and fatal neurodegenerative and metabolic diseases associated with misfolding and self-assembly of various proteins. Noncovalent interactions between these structural motifs and small molecules can, however, prevent this aggregation. Herein, five structurally different synthetic (Cz1-Cz4) and naturally occurring (Cz5, mahanimbine) fluorescent carbazole analogs are explored for their comparative amyloid aggregation inhibitory activities. Cz3 inhibited the amyloid deposition on the pancreatic β-cells of diabetic mice. Moreover, Cz3 and Cz5 also showed efficacy as the fluorescent cell (MIN6) imaging agents. Further structural modifications of these carbazoles may lead to development of low-cost and non-toxic therapeutic agents for Type 2 diabetes and other amyloidosis-related diseases.