Differential contribution of metal complexation and dimerization to the chemotherapeutic potential of bicyclen-Zn2II complex against human immunodeficiency virus

Abstract

1,1′-(m-Xylenediyl)-bis(1,4,7,10-tetraazacyclododecane)-Zn 2II complex (m-xylenediyl-bicyclen-Zn2II), a potent inhibitor of human immunodeficiency virus (HTV), was obtained from cyclen by a combination of dimerization and metal complexation. The ratio of median cytotoxic concentration against host cells (CC50) and median effective concentration against HIV cytopathogenicity (EC50), referred to as the selectivity index (SI), was regarded to be a measure of anti-HIV activity. These two chemical modifications contributed to a potent, in vitro anti-HIV activity of m-xylenediyl-bicyclen-Zn2II by respectively increasing the CC50 and decreasing the EC50 in comparison with those of cyclen.