Insight into the Biological Activity of Organometallic Acetylsalicylic Acid (Aspirin) Derivatives

Abstract

Despite of its long history as a drug, aspirin (acetylsalicylic acid, ASA) still fascinates investigators across the fields of chemistry, biology and medicine. In this regard, the development of aspirin derivatives with new, beneficial, biological properties still remains a challenge for chemists. This short review focuses on the chemistry and the biological activity of organometallic (those with metal-carbon bond) aspirin derivatives. Organometallic derivatization of aspirin has a profound influence on its mode of action and biological activity profile. In most organometallic ASA derivatives, the original ability for COX-1/2 acetylation persists, yet the acetylation sites are modified in comparison to that triggered by ASA itself. This alternation results from a combination of the electronic effect and the steric hindrance provided by the organometallic entity. Secondly, the metal center itself has a strong influence on biological activity through e. g., the ability for reactive oxygen species (ROS) generation in the cells. All of these examples, which are uncommon for ASA molecular action mechanisms, contribute to new pharmacological properties of organometallic ASA derivatives. These properties comprise anticancer, antiparasitic, and antibacterial activity.

Keywords: acetylsalicylic acid; anticancer activity; aspirin derivatives; bioorganometallics; metallodrugs.