caffeine-indan dimer

The caffeine-indan dimer, designated as **C8-6-I**, is a bifunctional experimental compound consisting of caffeine and indan (1-aminoindan) molecules linked by a **6-carbon chain**. This synthetic dimer was designed to cross the blood-brain barrier and exhibits neuroprotective properties by binding to **α-synuclein** (α-Syn) and preventing its aggregation and misfolding. The compound has demonstrated the ability to prevent α-synuclein-induced cell death and large α-synuclein foci formation in yeast models. Isothermal titration calorimetry studies indicate that the dimer has one binding site with α-synuclein and a binding constant of 5.3 × 10^4 M^−1. The compound has been tested in combination with the **adenosine A1 receptor agonist CPA** in animal studies, where it showed potential to attenuate α-synuclein upregulation and aggregation. Molecular docking simulations suggest that the dimer may induce a neuroprotective "loop" conformation in α-synuclein, potentially explaining its protective effects against neurodegeneration.