A comprehensive review on the development of chiral Cu, Ni, and Zn complexes as pharmaceutical agents over the past decades: Synthesis, molecular structure and biological activity.

Chirality is a fundamental and widespread geometric structural property in living organisms that most biomacromolecules including nucleic acids, proteins and enzymes, possess. Consequently, the development of chiral drugs capable of binding specific targets have gradually gained wide attention in recent decades due to their selective effects on a broad spectrum of biological events ranging from cell metabolism to cell fate. In this context, the synthesis of chiral compounds as promising therapeutic candidates has assumed a major role in drug discovery. Among them, chiral metal complexes have attracted considerable interest due to their unique and intriguing structural features that could enable overcoming side effects and drug-resistance phenomena of metalbased drugs currently in the market such as cisplatin. In the current scenario, an in-depth overview of non-platinum chiral complexes needs to be presented and carried forward. Therefore, in this perspective article, an update of the scientific development of bioactive chiral copper, zinc and nickel complexes have been reported since they have not been thoroughly reviewed so far. Specifically, we focused the article mainly on metal complexes containing chiral ligands (type 2 chirality) as in literature they are more numerous than those with chirality at the metal center (type 1 chirality). Herein, not only their biological activity but also their mechanism of action is summarized. Furthermore, in the final section of the article we have highlighted copper-based complexes as those with a superior biological activity profile and greater prospects for development as a drug.