Abstract
Catalysts are employed in many areas of research and development where they combine high efficiency with often astonishing selectivity for their respective substrates. In biology, biocatalysts are omnipresent. Enzymes facilitate highly controlled, sophisticated cellular processes, such as metabolic conversions, sensing and signalling, and are prominent targets in drug development. In contrast, the therapeutic use of catalysts per se is still rather limited. Recent research has shown that small molecule catalytic agents able to modulate the redox state of the target cell bear considerable promise, particularly in the context of inflammatory and infectious diseases, stroke, ageing and even cancer. Rather than being “active” on their own in a more traditional sense, such agents develop their activity by initiating, promoting, enhancing or redirecting reactions between biomolecules already present in the cell, and their activity therefore depends critically on the predisposition of the target cell itself. Redox catalysts, for instance, preferably target cells with a distinct sensitivity towards changes in an already disturbed redox balance and/or increased levels of reactive oxygen species. Indeed, certain transition metal, chalcogen and quinone agents may activate an antioxidant response in normal cells whilst at the same time triggering apoptosis in cancer cells with a different pre-existing “biochemical redox signature” and closer to the internal redox threshold. In pharmacy, catalysts therefore stand out as promising lead structures, as sensor/effector agents which are highly effective, fairly selective, active in catalytic, i.e., often nanomolar concentrations and also very flexible in their structural design.
Highlights
Catalysts take centre stage in many scientific disciplines and processes, from large scale industrial manufacture of substances such as ammonia to the common exhaust of petrol-powered automobiles where platinum catalysts detoxify some of the toxic by-products of fuel combustion
If one were to unleash the power of biocatalysis in therapy, the most obvious choice would probably involve the application of enzymes per se, as they are, literally, the natural choice of catalysts, being omnipresent in biological systems and evolved to highly efficient and at the same time selective macromolecules with impressive catalytic turnover rates and an amazing specificity for just one or a few substrates
In a pioneering study by Rabinkov and colleagues, the intra-venous application of such an alliinase-antibody hybrid prior to the administration of alliin substrate via various routes, including orally, successfully targeted an ovarian carcinoma in a mouse model in vivo [45]. It appears that once injected into the bloodstream, the enzyme-antibody hybrid swiftly located at the preferred site of action and that the cytotoxic allicin was formed primarily at this site
Summary
Catalysts take centre stage in many scientific disciplines and processes, from large scale industrial manufacture of substances such as ammonia to the common exhaust of petrol-powered automobiles where platinum catalysts detoxify some of the toxic by-products of fuel combustion. The catalyst acts on the kinetics, not on the thermodynamics of the reaction This means that: (a) its actions rely critically on the presence of suitable substrates and (b) catalysts may seemingly initiate, promote, enhance or even redirect energetically favourable reactions, yet are unable to trigger energetically unfavourable reactions. Drugs containing enzyme inhibitors are legend, such as penicillins which inhibit a specific transpeptidase and serve as broad-spectrum antibiotics [16] Such inhibitors are prominent in other fields, for instance as antiviral drugs, where zidovudine and lamivudine inhibit nucleotide reverse transcriptase and serve in the treatment of human immunodeficiency virus (HIV), and in cancer research, where one only needs to consider methotrexate, which inhibits tetrahydrofolate dehydrogenase and impairs DNA synthesis and cell proliferation [17,18,19]. As part of this review, and as prelude to the Special Issue on “Small molecule catalysts with therapeutic potential”, we will briefly consider some of these highlights with the aim to foster a wider understanding of their enormous potential and potential future applications
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