Organometallic 3-(1H-Benzimidazol-2-yl)-1H-pyrazolo[3,4-b]pyridines as Potential Anticancer Agents

In undergraduate level organometallic chemistry courses students are usually taught that organometallic compounds are toxic and unstable in air and water. While this is true of many complexes, some are also non-toxic and stable in air and water. Indeed, bioorganometallic chemistry, the study of biomolecules or biologically active molecules that contain at least one carbon directly bound to a metal, is a thriving subject, and air and water stability is a general pre-requisite. This interdisciplinary field is located at the borderline between chemistry, biochemistry, biology and medicine. In this tutorial review, various aspects of bioorganometallic chemistry are introduced, with the main emphasis on medicinal organometallic compounds. Organometallic therapeutics for cancer, HIV and malaria and other medicinal applications are described. It is also shown how rational ligand design has led to new improved therapies much in the same way that an organometallic chemist working in catalysis will design new ligands for improved activities. Show more

The field of medicinal inorganic chemistry is rapidly advancing. In particular organometallic complexes have much potential as therapeutic and diagnostic agents. The carbon-bound and other ligands allow the thermodynamic and kinetic reactivity of the metal ion to be controlled and also provide a scaffold for functionalization. The establishment of structure-activity relationships and elucidation of the speciation of complexes under conditions relevant to drug testing and formulation are crucial for the further development of promising medicinal applications of organometallic complexes. Specific examples involving the design of ruthenium and osmium arene complexes as anticancer agents are discussed. Show more

The pursuit for drugs that inhibit cyclin-dependent kinases (CDKs) has been an intense area of research for more than 15 years. The first-generation inhibitors, Flavopiridol and CY-202, are in late-stage clinical trials, but so far have demonstrated only modest activity. Several second-generation inhibitors are now in clinical trials. Future approaches to determine clinical benefit need to incorporate both the lessons learned from these early compounds and information recently obtained from the genetic analysis of CDKs in preclinical models. Here we discuss key concepts that should be considered when validating the clinical utility of CDK inhibitors in cancer therapy. Show more