Phytochemicals include a huge array of plant products relevant for their biological activities. Among these, polyphenols have extensively been studied because of their ecological roles in plants and healthy properties relevant to humans. In particular, the diets rich in plant foods have been associated to a reduced risk of chronic degenerative diseases (cardiovascular disease, neurological disorders and some types of cancer), probably due to their high content of bioactive polyphenols as well as of other phytochemicals (carotenoids, glucosinolates, phytosterols…). In this chapter, we briefly introduce polyphenols, both from the plant and the human perspective, focusing on their antioxidant activity.

Flavonoids are a major class of plant phenolics that are widely distributed in the human diet and have been related to health promotion. They may occur in their natural sources in free forms (aglycones), as glycosylated or acylated derivatives, or as oligomeric and polymerized structures. This structural diversity affects their physicochemical behaviour and complicates their analysis. Thus, there is not a single standardized procedure that can be recommended for all flavonoid groups and/or type of samples, and the procedures have to be optimized depending on the nature of the sample and the target analytes. Furthermore, when dealing with the analysis of flavonoids biological samples (i.e., human and animal fluids and tissues) some differential aspects have to be taken into account; the nature of the compounds that can be found in those samples may differ from that present in plants and food, and flavonoids and metabolites occur in much lower concentrations, which make their analysis still more challenging. In this review the main techniques for extraction and analysis of flavonoids in foodstuffs and biological fluids are revised. Discussion on available databases including data on the contents of flavonoids in foods, useful for the estimation of their dietary intake, and emerging biomarkers of flavonoid consumption is also made.

The cannabinoid system is represented by two principal receptor subtypes, termed CB1 and CB2, along with several endogenous ligands. In the central nervous system it is involved in several processes. CB1 receptors are mainly expressed by neurons and their activation is primarily implicated in psychotropic and motor effects of cannabinoids. CB2 receptors are expressed by glial cells and are thought to participate in regulation of neuroimmune reactions. This review aims to highlight several reported properties of cannabinoids that could be used to inhibit the adverse neuroinflammatory processes contributing to Parkinson’s disease and possibly other neurodegenerative disorders. These include anti-oxidant properties of phytocannabinoids and synthetic cannabinoids as well as hypothermic and antipyretic effects. However, cannabinoids may also trigger signaling cascades leading to impaired mitochondrial enzyme activity, reduced mitochondrial biogenesis, and increased oxidative stress, all of which could contribute to neurotoxicity. Therefore, further pharmacological studies are needed to allow rational design of new cannabinoid-based drugs lacking detrimental in vivo effects.

Epipolythiodioxopiperazines (ETPs), characterized by a unique bridged disulfide or polysulfide dioxopiperazine six-membered ring (namely 2,5-epipolythiopepeazine-3,6- dione ring system), occur in a diversity of fungi. In recent years, ETPs drawn increasing research attentions from the field of chemistry and biological due to their broad spectra of bioactivities including antitumor, antiviral and antimicrobial activities. From this point of view, this review summarized diverse natural sources that produce ETPs, the synthetic chemistry of ETPs and an overview of promising bioactivities exhibited by some well studied ETPs. The plausible biosynthetic hypotheses of ETPs and some new results on antitumor activity of ETPs are also reviewed.

Oxadiazine scaffold-based compounds are undoubtedly an important class of heterocyclic derivatives, which always present diverse bioactivities including cardiovascular, antitumor, antiviral, anti-leishmanial, antibacterial, antimicrobial, monoamine oxidase inhibition, acricidal, insecticidal, plant-growth regulating activities and chitin biosynthesis inhibitions. With the development of organic synthesis, versatile features of oxadiazine ring have emerged, so here we have reviewed the recent advances of oxadiazine-based heterocyclic derivatives mainly including preparation, transformation and biological properties, and this report is also an updated version of our previous review with modifications.

Tyrosine kinase receptors have been shown to play an important role in epithelial thyroid tumor growth and angiogenesis. Thyroid cancers commonly present oncogene mutations involved in MAPK kinase pathway like BRAF and RET; they are also frequently dependent from VEGF stimuli. Preliminary clinical experiences suggest a promising role of sunitinib (a tyrosine kinase inhibitor) for the treatment of advanced thyroid cancers. This chapter deals with the available data on the effect of sunitinib in the treatment of metastatic, radioiodine refractory thyroid cancers.

Mitochondria has attracted the attention as a promising pharmacological target because the impairment of electron transport chain (ETC) function by ROS overproduction and disturbances in the process of mitochondrial quality control (i.e. mitochondrial dynamics (mitochondria fusion/fission) and mitophagy) play a prominent role in the etiology of highly prevalent diseases like diabetes, hypertension, neurodegeneration, among others. This has led to the development of mitochondriatargeted antioxidants in order to achieve a better antioxidant effect at the mitochondrial milieu. However, these molecules had shown some disappointing outcomes, which may be the result for a need of a better understanding of the actions of these antioxidant molecules over mitochondria. To achieve this, it must be considered the interplay between the sources of ROS during disease, the chemical interconversions of ROS and their differential reactivity with ETC components. Besides, both mitochondrial dynamics and mitophagy are regulated by the fitness of mitochondrial function and ROS signaling. Thus, although beneficial under some context, depletion of ROS generation might be also detrimental by impairing the signaling allowing the preservation of healthy mitochondrial function through the elimination of damaged organelles. This review contrasts all these aspects of mitochondrial function with available data about mitochondrial damage in specific diseases to give an insight into the importance of ROS chemistry in the rational desing of such molecules, putting emphasis in the case of MitoQ.