A Cisplatin-Selective Fluorescent Probe for Real-Time Monitoring of Mitochondrial Platinum Accumulation in Living Cells.

Mitochondria have emerged as important targets for cisplatin in cancer therapy. Apart from cisplatin, anticancer Pt complexes based on similar scaffolds have also been developed to target mitochondria. Yet cellular processing of cisplatin or these mitochondria-targeting Pt analogues remained unexplored, largely due to a lack of tools capable of probing these Pt drugs within an intracellular environment.

Development of a Pre-assembled Through-Bond Energy Transfer (TBET) Fluorescent Probe for Ratiometric Sensing of Anticancer Platinum(ll) Complexes.

Fluorescence microscopy has emerged as an attractive technique to probe the intracellular processing of Pt-based anticancer compounds. Herein, we reported the first through-bond energy transfer (TBET) fluorescent probe NPR1 designed for sensitive detection and quantitation of Pt complexes. The novel TBET probe was successfully applied for ratiometric fluorescence imaging of anticancer Pt complexes such as cisplatin and JM118 in cells.

A Ratiometric Fluorescent Probe for Cisplatin: Investigating the Intracellular Reduction of Platinum(IV) Prodrug Complexes.

The Pt prodrug strategy has emerged as an excellent alternative to tackle the problems associated with conventional Pt drug therapy. However, there is a lack of tools to study how this new class of Pt drugs are processed at the cellular level. Herein, we report the first ratiometric probe for cisplatin detection and use it to investigate Pt anticancer complexes in biological systems.

Pre-Assembled Coumarin-Rhodamine Scaffold for Ratiometric Sensing of Nitric Oxide and Hypochlorite.

A new pre-assembled ratiometric sensing platform was constructed from a coumarin donor and a rhodamine acceptor designed for through-bond energy transfer (TBET). A phenylacetylene linker was installed to disrupt the planarity of the extended conjugated system but retaining the efficient energy transfer between the donor and acceptor motifs. To demonstrate its versatility as a sensing platform, we conjugated recognition motifs through amide coupling reactions to yield two TBET chemosensors capable of sensing either endogenously produced NO and ClO .

Structure-activity relationship studies on rhodamine B-based fluorogenic probes and their activation by anticancer platinum(II) compounds.

Fluorescence microscopy has emerged as an attractive technique for imaging intracellular Pt species arising from exposure to clinical anticancer drugs such as cisplatin. A rhodamine-B based fluorogenic probe termed Rho-DDTC can be activated selectively in the presence of Pt(II) compounds, and possesses the ability to discriminate Pt(II) species from Pt(IV) carboxylate prodrug complexes, thereby providing a unique platform to investigate the reduction of these Pt(IV) complexes after cell entry. In this report, we seek to establish the mechanism of activation of Rho-DDTC through a structure-activity relationship study on its structural analogues.

Platinum(IV) Carboxylate Prodrug Complexes as Versatile Platforms for Targeted Chemotherapy.

Kinetically-inert Pt(IV) carboxylate complexes have emerged in recent years as candidates for the development of next-generation platinum anticancer drugs. Being native prodrugs of clinically-important Pt(II) chemotherapeutic agents, the Pt(IV) scaffold can be exploited to incorporate additional functionalities while keeping the Pt(II) pharmacophore intact. This mini-review examines recent work performed to illuminate the mechanism of Pt(IV) prodrug activation and their use as versatile platforms for targeted chemotherapy.

Rational design of selective organoruthenium inhibitors of protein tyrosine phosphatase 1B.

Protein tyrosine phosphatases (PTPs) belong to a large family of important regulatory enzymes involved in vital mammalian signaling pathways. Selective inhibitors of PTPs are highly valuable from a therapeutic standpoint given their association with various pathological conditions. One such target is PTP-1B which has previously been linked to diabetes and cancer.

Photoreactive gold(I) macrocycles with diphosphine and trans,trans-muconate ligands.

A pair of trans,trans-muconate ligands have been successfully aligned in two novel Au(I) macrocycles by design from phosphino metal precursors that undergo photochemical cycloaddition reactions quantitatively, resulting in the formation of cyclooctadiene derivatives.