Anticancer activity and DNA interaction of bis(pyridyl)allene-derived metal complexes

Abstract

Abstract The constant need for novel drugs has prompted the scientific community to explore alternative structures to natural products and small and medium size organic compounds used in classic medicinal and pharmaceutical chemistry. Since the discovery of cisplatin, organometallic compounds have revealed great potential as metallodrugs and their development has exponentially grown in recent years. In this manuscript, we describe our efforts towards the synthesis of new metallodrugs by reaction of bis(pyridyl)allenes and metal complexes. Two classes of compounds are presented: one in which the allene structure is intact and the metal (Pd(II), Pt(IV) or Au(III)) coordinates to the pyridine-nitrogens; and another, in which one of the pyridines cyclises into a gold-activated allene to form β-N-stabilised gold carbenes. Both classes of compounds are active catalysts in important organic reactions, and are also promising antimicrobial, antifungal and anticancer agents. In this work, we describe the promising anticancer activity, against breast cancer cells, of the gold carbene complexes, and preliminary studies of their interaction with DNA, including non-canonical DNA structures. Our results have revealed an unusual selective stabilisation of hTeloC i-motif by one of the Au(III) carbene complexes, that opens up exciting opportunities for further development of novel DNA-binding metallodrugs.