School of Physical and Chemical Sciences Te Kura Matū Seminar Series

Novel Structural Motifs and Biophysical Investigations to Delineate Biomolecule Interactions in the Quest for Organometallic Anticancer Agents

Speaker

Christian G. Hartinger

Institute

University of Auckland, Auckland, New Zealand

Time & Place

Wed, 30 Oct 2019 12:00:00 NZDT in Room 701, West Building

All are welcome

Abstract

Bioorganometallic chemistry is a thriving field of research and in particular the development of anticancer drugs based on organometallic moieties, often with bioactive co-ligands, has received a lot of attention in recent years.1-3 While the modes of action of anticancer metallodrugs are crucially dependent on their interactions with biological molecules, we often lack an understanding of the targets and how the complexes are metabolized in biological environment.

Many established chemotherapeutics have low selectivity for tumor tissue and cause adverse effects, which limit the dose that can be administered. Our research aims to develop targeted and targeting drugs, using organometallic moieties to interact selectively with a biomolecular target or to be selectively transported to and accumulated in tumor tissue (Figure 1).1 The coordination of bioactive ligands to metal centers may result in multimodal anticancer agents with ideally synergistic activity between the ligand and the metal center. Such approaches have led to compounds with significant anticancer activity.3,4 This presentation will focus on the introduction of novel ligand structures and their organometallic complexes studied in my group, such as N-heterocyclic carbene (NHC)-based and related mono- and bidentate ligand structures. Surprising behavior in presence of biomolecules, studied by a combination of biophysical methods, has led us to a deeper understanding of their modes of action and the impact of the nature of the complex on the bioactivity.4

Hartinger_image_20190522

Figure 1. Design and biomolecule interaction studies of novel organometallic anticancer agents.

 

References

[1] C. G. Hartinger, N. Metzler-Nolte, P. J. Dyson, Organometallics, 31, 5677 (2012)

[2] P. Chellan, P. J. Sadler, Philos. Trans. R. Soc., A, 373, 20140182 (2015)

[3] M. Kubanik, Lam N. Y. S., Holtkamp H. U., Soehnel T., Anderson R. F., Jamieson S. M. F., Hartinger C. G., Chem. Commun., 54, 992 (2018).

[4] M. P. Sullivan, M. K. Nieuwoudt, G. A. Bowmaker, N. Y. S. Lam, D. Truong, D. C. Goldstone, C. G. Hartinger, Chem. Commun., 54, 6120 (2018).

 

All Welcome

Biography

Read more about Christian G. Hartinger