Metal‐Based Catalytic Drug Development for Next‐Generation Cancer Therapy

Abstract

Considering the high increase in mortality caused by cancer in recent years, cancer drugs with novel mechanisms of anticancer action are urgently needed to overcome the drawbacks of platinum‐based chemotherapeutics. Recently, in the area of metal‐based cancer drug development research, the concept of catalytic cancer drugs has been introduced with organometallic RuII, OsII, RhIII and IrIII complexes. These complexes are reported as catalysts for many important biological transformations in cancer cells such as nicotinamide adenine dinucleotide (NAD(P)H) oxidation to NAD+, reduction of NAD+ to NADH, and reduction of pyruvate to lactate. These unnatural intracellular transformations with catalytic and nontoxic doses of metal complexes are known to severely perturb several important biochemical pathways and could be the antecedent of next‐generation catalytic cancer drug development. In this concept, we delineate the prospects of such recently reported organometallic RuII, OsII, RhIII and IrIII complexes as future catalytic cancer drugs. This new approach has the potential to deliver new cancer drug candidates.

Designing a multitarget In(iii) compound to overcome the resistance of lung cancer cells to cisplatin

“…1,4 Thus, there is an urgent need to explore novel strategies for designing next-generation metal agents to reverse the resistance of cancer cells. 5,6…”

Photocatalytic glucose-appended bio-compatible Ir(iii) anticancer complexes

“…Metal-based catalytic anti-cancer drugs are evolving as a new strategy for cancer treatment. 1,2 Two advantages of this approach are (i) minimization of drug concentrations to reduce toxicity and off-target side effects, and (ii) novel mechanisms of action to overcome drug resistance, which is becoming a problem for Pt(II) chemotherapeutics. 1,2 Catalytic Rh(III), Ir(III) and Os(II) organometallic complexes can alter the intracellular redox and metabolic balance, 1,2 for example, by modifying pyruvate/lactate or NADH/NAD + (reduced and oxidized nicotinamide adenine dinucleotide) ratios within cancer cells.…”

“…1,2 Two advantages of this approach are (i) minimization of drug concentrations to reduce toxicity and off-target side effects, and (ii) novel mechanisms of action to overcome drug resistance, which is becoming a problem for Pt(II) chemotherapeutics. 1,2 Catalytic Rh(III), Ir(III) and Os(II) organometallic complexes can alter the intracellular redox and metabolic balance, 1,2 for example, by modifying pyruvate/lactate or NADH/NAD + (reduced and oxidized nicotinamide adenine dinucleotide) ratios within cancer cells. [1][2][3][4][5] The introduction of photoactivated catalysts offers the possibility of increasing selectivity for cancer cells versus normal tissues with spatially-directed light irradiation.…”

“…1,2 Catalytic Rh(III), Ir(III) and Os(II) organometallic complexes can alter the intracellular redox and metabolic balance, 1,2 for example, by modifying pyruvate/lactate or NADH/NAD + (reduced and oxidized nicotinamide adenine dinucleotide) ratios within cancer cells. [1][2][3][4][5] The introduction of photoactivated catalysts offers the possibility of increasing selectivity for cancer cells versus normal tissues with spatially-directed light irradiation. Hence the concept of photo-catalytic cancer drugs is attractive.…”

“…Hence the concept of photo-catalytic cancer drugs is attractive. 1,2 There appear to be only two literature reports to date on the design of such agents, 6,7 both Ir(III) photo-catalysts chosen for their rich photochemistry. Although the reported Ir(III) catalysts show good photo-induced intracellular NADH oxidation and anticancer activity, their poor aqueous solubility limited progress with drug development.…”