**1. Introduction**

The compounds produced by nature exhibit a grea<sup>t</sup> diversity of chemical structures as a result of the long, selective and evolutive process of species [1], and they constitute the active principles of natural products which have always contributed, a lot, to improve human living conditions [2]. As natural products have widespread uses in traditional medicine [3–5], and a wide range of biological effects demonstrated scientifically, they possess high scientific and industrial value [6–9].

The properties demonstrated by natural compounds constantly encourage scientific research in aspects that lead to significant advances in the identification of new natural compounds, evaluation of the biological activity displayed, understanding of how they cause a biological effect, in the development of new applications and in all cases with beneficial results for humanity.

Despite very significant advances in medicine, many diseases such as cancer, infections, diabetes and cardiovascular diseases remain without affordable, effective and safe therapy. Due to this, the most frequently explored area with relevant results is the development of new drugs from natural sources [7,8,10–14], with natural product-based new drugs being 51% of small molecules approved and launched in the market between 1981 and 2014 [15].

The demand for natural antimicrobial agents and anticancer drugs is a very active research point [16–20] since cancer and infectious diseases are a significant cause of mortality worldwide [21]. Moreover, the World Health Organization predicts that the incidence of cancer will continue to rise to over 11 million in 2030 [22]. More than 1700 clinical trials involving the natural vinca alkaloids to treat cancer are registered currently on the clinicaltrials.gov platform [23]. Furthermore, the resistance and undesirable side effects of antibiotics and antineoplastic agents used in the clinic [24,25] have become pressing problems, leading to a continuous search for new inhibitors with new mechanisms of action.

The application of natural compounds as antioxidant agents is also a hot topic [26–29], once several diseases are, at least partially, a result of free radicals' imbalance [26,30,31]. Overproduction of oxygen free radicals, when associated with the deficiency in antioxidant repair or defence mechanisms, will cause oxidative damage leading to disease development like cancer, inflammation, diabetes, cardiovascular and aging-associated diseases [26,30–32].

Natural products are also applied as an ingredient in cosmetic preparations [33,34] and in the food industry since they exhibit useful preservative properties [35,36].

The limited availability of a natural product is a di fficulty when it is a promising molecule for an application. Thus, recently, it has been proposed that several techniques that can improve the natural product yield. It is the case of metabolomics, enable the rapid identification of novel compounds in complex mixtures of natural products, metabolic engineering of cells endowed with the ability of overproduction of new products and metagenomics exploring novel metabolites from microorganisms present in several environments but which remain recalcitrant to culturing [37–39].

Natural compounds are privileged structures because of their structural diversity and multiple biological activities. They are undoubtedly the ideal compounds for the rational design of new drugs and the development of new chemical entities with therapeutic potential [8,14]. Thus, research on natural compounds is necessary and very welcome.

This Special Issue is dedicated to present the most recent results about the development of natural compounds applications. Ten original research works, organized by applications, and two reviews are included in this Special Issue. Each of them contributes to the knowledge advance, insofar as they present new applications for known products, new methodologies to obtain new products or the evaluation of a given application, with the applications related to health promotion being the most frequently considered.
