Thiophene-based water-soluble fullerene derivatives as highly potent antiherpetic pharmaceuticals

Abstract

Here we report the Friedel–Crafts arylation of chlorofullerenes C₆₀Cl₆ and C₇₀Cl₈ with thiophene-based methyl esters. While C₆₀Cl₆ formed expected C_s-C₆₀R₅Cl products, C₇₀Cl₈ demonstrated a tendency for both substitution of chlorine atoms and addition of an extra thiophene unit, thus forming C_s-C₇₀R₈ and C₁-C₇₀R₉H compounds. The synthesized water-soluble C₆₀ and C₇₀ fullerene derivatives with thiophene-based addends demonstrated high activity against a broad range of viruses, including human immunodeficiency virus, influenza virus, cytomegalovirus, and herpes simplex virus. The record activity of C₇₀ fullerene derivatives against herpes simplex virus together with low toxicity in mice makes them promising candidates for the development of novel non-nucleoside antiherpetic drugs.