Neurodegeneration is a gradual decay process leading to the depletion of neurons in both the central and peripheral nervous systems, ultimately resulting in cognitive dysfunctions and the deterioration of brain functions, alongside a decline in motor skills and behavioral capabilities. Neurodegenerative disorders (NDs) impose a substantial socio-economic strain on society, aggravated by the advancing age of the world population and the absence of effective remedies, predicting a negative future. In this context, the urgency of discovering viable therapies is critical and, despite significant efforts by medicinal chemists in developing potential drug candidates and exploring various small molecules as therapeutics, regrettably, a truly effective treatment is yet to be found. Nitrogen heterocyclic compounds, and particularly those containing the indole nucleus, which has emerged as privileged scaffold, have attracted particular attention for a variety of pharmacological applications. This review analyzes the rational design strategy adopted by different research groups for the development of anti-neurodegenerative indole-based compounds which have the potential to modulate various molecular targets involved in NDs, with reference to the most recent advances between 2018 and 2023.

The translocator protein (TSPO) is predominately localized on the outer mitochondrial membrane in steroidogenic cells. In the brain, TSPO expression, low under normal conditions, results upregulated in response to glial cell activation, that occurs in neuroinflammation. As a consequence, TSPO has been extensively studied as a biomarker of such conditions by means of TSPO-targeted radiotracers. Although [¹¹C]-PK11195, the prototypical TSPO radioligand, is still widely used for in vivo studies, it is endowed with severe limitations, mainly low sensitivity and poor amenability to quantification. Consequently, several efforts have been focused on the design of new radiotracers for the in vivo imaging of TSPO. The present review will provide an outlook on the latest advances in TSPO radioligands for neuroinflammation imaging. The final goal is to pave the way for (radio)chemists in the future design and development of novel effective and sensitive radiopharmaceuticals targeting TSPO.

Auranofin (AF) is an oral gold(I) compound with a well-known pharmacological profile, currently used in the treatment of some severe forms of rheumatoid arthritis. Over the last twenty years, AF has also been repurposed as an antitumor, antiviral, and antibacterial drug. In this context, this review provides an updated overview of all clinical trials investigating AF for the treatment of various pathologies, either as monotherapy or in combination with other agents. We started summarizing the rationale behind repurposing AF in oncology, including its ability to inhibit thioredoxin reductase (TrxR) and disrupt redox homeostasis, leading to selective cytotoxicity in cancer cells. Clinical data from trials across a range of tumors are reviewed, highlighting safety profiles, dosing regimens, pharmacokinetics, and observed therapeutic outcomes. Then, we discussed the synergistic effects observed when AF is combined with chemotherapeutics, targeted therapies, or immune modulators. Then, an overview concerning the trials involving AF in non-oncological settings is also provided. Despite promising preclinical results, clinical translation remains in early stages, with most trials still in phase I or II. Nevertheless, emerging evidence supports continued exploration of AF-based therapies to address unmet medical needs.

Auranofin (AF) is an oral gold(I) compound with a well-known pharmacological profile, currently used in the treatment of some severe forms of rheumatoid arthritis. Over the last twenty years, AF has also been repurposed as antitumor, antiviral, and antibacterial drug. In this context, this review provides an updated overview of all clinical trials investigating AF for the treatment of various pathologies, either as monotherapy or in combination with other agents. We started summarizing the rationale behind repurposing AF in oncology, including its ability to inhibit thioredoxin reductase (TrxR) and disrupt redox homeostasis, leading to selective cytotoxicity in cancer cells. Clinical data from trials across a range of tumors are reviewed, highlighting safety profiles, dosing regimens, pharmacokinetics, and observed therapeutic outcomes. Then, we discussed the synergistic effects observed when AF is combined with chemotherapeutics, targeted therapies, or immune modulators. Then, an overview concerning the trials involving AF in non-oncological setting is also provided. Despite promising preclinical results, clinical translation remains in early stages, with most trials still in phase I or II. Nevertheless, emerging evidence supports continued exploration of AF-based therapies to address unmet medical needs.