Christian G. Hartinger

Bio: Christian G. Hartinger is an academic researcher from University of Auckland. The author has contributed to research in topics: Ruthenium & Ligand. The author has an hindex of 67, co-authored 248 publications receiving 15892 citations. Previous affiliations of Christian G. Hartinger include University of Vienna & École Polytechnique Fédérale de Lausanne.

Bioorganometallic chemistry—from teaching paradigms to medicinal applications

Abstract: 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.

Antitumour metal compounds: more than theme and variations.

Abstract: Triggered by the resounding success of cisplatin, the past decades have seen tremendous efforts to produce clinically beneficial analogues. The recent achievement of oxaliplatin for the treatment of colon cancer should, however, not belie the imbalance between a plethora of investigated complexes and a very small number of clinically approved platinum drugs. Strategies opening up new avenues are increasingly being sought using complexes of metals other than platinum such as ruthenium or gallium. Based on the chemical differences between these metals, the spectrum of molecular mechanisms of action and potential indications can be broadened substantially. Other approaches focus on complexes with tumour-targeting properties, thereby maximizing the impact on cancer cells and minimizing the problem of adverse side effects, and complexes with biologically active ligands.

Antitumour metal compounds: more than theme and variations

Abstract: Triggered by the resounding success of cisplatin, the past decades have seen tremendous efforts to produce clinically beneficial analogues. The recent achievement of oxaliplatin for the treatment of colon cancer should, however, not belie the imbalance between a plethora of investigated complexes and a very small number of clinically approved platinum drugs. Strategies opening up new avenues are increasingly being sought using complexes of metals other than platinum such as ruthenium or gallium. Based on the chemical differences between these metals, the spectrum of molecular mechanisms of action and potential indications can be broadened substantially. Other approaches focus on complexes with tumour-targeting properties, thereby maximizing the impact on cancer cells and minimizing the problem of adverse side effects, and complexes with biologically active ligands.

KP1019, a new redox-active anticancer agent--preclinical development and results of a clinical phase I study in tumor patients.

Abstract: The promising drug candidate indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019) is the second Ru-based anticancer agent to enter clinical trials. In this review, which is an update of a paper from 2006 (Hartinger et al., J. Inorg. Biochem. 2006, 100, 891-904), the experimental evidence for the proposed mode of action of this coordination compound is discussed, including transport into the cell via the transferrin cycle and activation by reduction. The results of the early clinical development of KP1019 are summarized in which five out of six evaluated patients experienced disease stabilization with no severe side effects.

I and i

Abstract: There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality. Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Molecular mechanisms of cisplatin resistance

Abstract: Platinum-based drugs, and in particular cis-diamminedichloroplatinum(II) (best known as cisplatin), are employed for the treatment of a wide array of solid malignancies, including testicular, ovarian, head and neck, colorectal, bladder and lung cancers. Cisplatin exerts anticancer effects via multiple mechanisms, yet its most prominent (and best understood) mode of action involves the generation of DNA lesions followed by the activation of the DNA damage response and the induction of mitochondrial apoptosis. Despite a consistent rate of initial responses, cisplatin treatment often results in the development of chemoresistance, leading to therapeutic failure. An intense research has been conducted during the past 30 years and several mechanisms that account for the cisplatin-resistant phenotype of tumor cells have been described. Here, we provide a systematic discussion of these mechanism by classifying them in alterations (1) that involve steps preceding the binding of cisplatin to DNA (pre-target resistance), (2) that directly relate to DNA-cisplatin adducts (on-target resistance), (3) concerning the lethal signaling pathway(s) elicited by cisplatin-mediated DNA damage (post-target resistance) and (4) affecting molecular circuitries that do not present obvious links with cisplatin-elicited signals (off-target resistance). As in some clinical settings cisplatin constitutes the major therapeutic option, the development of chemosensitization strategies constitute a goal with important clinical implications.