Targeted synthesis and biological activity of polypharmacophoric agents for the treatment of neurodegenerative diseases

Resumo

Synthetic approaches to the design of new multitarget agents for the treatment of neurodegenerative diseases are surveyed. These approaches are based on the conjugation of the pharmacophoric indole, phenothiazine, and aminoadamantane moieties via 1-oxopropylene and 2-hydroxypropylene spacers using reactions of acrylate- and epoxide-containing pharmacophores with tetrahydro-γ-carbolines, cycloalkaneindoles, carbazoles, and aminoadamantanes. The review considers data on biological activity of the compounds assessed within a complex screening system. This system includes neurotransmitter targets associated with cognitive compensation, such as cholinesterases and glutamate receptors, mitochondria, the influence on which can provide neuroprotective effects, and microtubules, the stabilization of which leads to the improvement of axonal transport. The ability of the compounds to act as free-radical scavengers was evaluated. Types of polypharmacophoric compounds promising for further development are proposed.