Harnessing Endogenous Formate for Antibacterial Prodrug Activation by in cellulo Ruthenium-Mediated Transfer Hydrogenation Reaction

The abundance and evolving pathogenic behavior of bacterial microorganisms give rise to antibiotic tolerance and resistance which pose a danger to global public health. New therapeutic strategies are needed to keep pace with this growing threat. We propose a novel approach for targeting bacteria by harnessing formate, a cell metabolite found only in particular bacterial species, to activate an antibacterial prodrug and selectively inhibit their growth.

A structure-based mechanism of cisplatin resistance mediated by glutathione transferase P1-1

Cisplatin [cis-diamminedichloroplatinum(II) (cis-DDP)] is one of the most successful anticancer agents effective against a wide range of solid tumors. However, its use is restricted by side effects and/or by intrinsic or acquired drug resistance.

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

The PtIV prodrug strategy has emerged as an excellent alternative to tackle the problems associated with conventional PtII drug therapy. However, there is a lack of tools to study how this new class of PtIV drugs are processed at the cellular level.

Apoptosis-independent organoruthenium anticancer complexes that overcome multidrug resistance: self-assembly and phenotypic screening strategies

Multidrug resistance is a major impediment to chemotherapy and limits the efficacies of conventional anticancer drugs. A strategy to bypass multidrug resistance is to develop new drug candidates capable of inducing apoptosis-independent programmed cell death. However, cellular pathways implicated in alternative programmed cell death are not well-elucidated and multifactorial, making a target-based discovery approach a challenge.

Structural tuning of organoruthenium compounds allows oxidative switch to control ER stress pathways and bypass multidrug resistance

Multidrug resistance (MDR) is a major impediment to the success of chemotherapy in many cancer types. One particular MDR mechanism is the inherent or acquired adaptation of the cellular survival pathways that render malignant cells resistant to apoptotic cell death. Since most drugs act through apoptosis, compounds capable of inducing alternative forms of programmed cell death (PCD) can potentially be harnessed to bypass MDR.

Induction of Immunogenic Cell Death by Chemotherapeutic Platinum Complexes (VIP)

There is compelling evidence suggesting that the immune-modulating effects of many conventional chemotherapeutics, including Pt agents, play a crucial role in achieving clinical response. One way in which chemotherapeutics can engage a tumour-specific immune response is by triggering an immunogenic mode of tumour cell death (ICD) which then acts as a de facto anticancer vaccine. Although a mainstay of chemotherapy, there has not been a systematic attempt to screen both existing and upcoming Pt agents for their ICD ability.

Immuno-Chemotherapeutic Platinum(IV) Prodrugs of Cisplatin as Multimodal Anticancer Agents

There is growing consensus that the clinical therapeutic efficacy of some chemotherapeutic agents depends on its off-target immune-modulating effects. Pt anticancer drugs have earlier been identified to be potent immunomodulators of both the innate immune system as well as the adaptive immune system. Nevertheless, there has been little development in the rational design of Pt-based chemotherapeutic agents to exploit their immune-activating capabilities. FPR1/2 receptors are highly expressed in immune cells as well as many metastatic cancers.

A Fluorescent Probe for Investigating the Activation of Anticancer Platinum(IV) Prodrugs Based on the Cisplatin Scaffold

A fluorescent probe was engineered to detect clinically-important platinum drug cisplatin within a complex cellular environment, thus providing a direct means of visualizing cell entry as well as activation of platinum(IV) prodrugs in cancer cells.

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