# Secondary Metabolites and Their Applications
## 2 Contributions
The concentration of those compounds and differences in the sensitivity of the plant models are key to their phytotoxic action. Additionally, a mixture of both compounds at low concentrations had synergistic effects concerning phytotoxic activity. Shedding light on the mechanisms of action that justify the observed secondary metabolite bioeffects is an essential point where more research is needed before it can advance towards clinical therapy. The secondary metabolite thymoquinone can be extracted from the seed oil of _Nigella sativa_ L. (black seed oil) and exhibits several biological activities [13], among which are relevant antitumor properties, and has already been the subject of clinical studies (ClinicalTrials.gov Identifier: NCT03208790). However, its mechanism of action is not yet fully understood. [PERSON] et al. [14] make a very significant contribution to clarifying this point. They show that thymoquinone, unlike doxorubicin, specifically targets the oncogene UHRF1. Probably through the downregulation of HAUSP, thymoquinone induces the rapid ubiquitination of UHRF1, an essential event for the induction of cancer cell apoptosis without, however, affecting the Bcl-2 oncogene [14]. The total synthesis of natural secondary metabolites contributes not only to confirm the proposed chemical structure of the natural compound but also to satisfy the demand for more compounds for different applications without degrading the environment. Thus, the work by [PERSON] et al. [15] is a great contribution to the development of new applications for the secondary metabolite Aaptoline B, a pyrroloquinoline alkaloid extracted from the marine sponge _Aaptos aaptos_ Schmidt and considered a privileged scaffold in drug discovery. The authors suggest a short but comprehensive and efficient synthetic process for Aaptolin B and demonstrate, using _Caenorhabditis elegans_ as a model of the [PERSON]'s disease-like neuronal environment, that this compound exhibits a neuroprotective effect [15]. Thus, the door is open for investigation into a new application for this secondary metabolite. Laboratory synthesis is not the only strategy applied to obtain new and greater amounts of bioactive secondary metabolites. _Streptomyces_ is a group of Gram-positive bacteria capable of biosynthesisizing a wide range of natural compounds from different families, with different commercial applications and high economic value [16]. Doxorubicin, an antitumor antibiotic, and avermectin, used to treat parasitic worms and insect pests, are just two well-known examples. However, the potential of these microorganisms to produce secondary metabolites is much greater than achieved so far. The problem is, under laboratory conditions, many of the genes responsible for this biosynthesis remain silent. Heterologous biosynthesis has been an applied approach to overcome this limitation. [PERSON] et al. [17] publish in this Special Issue a review of the literature on the latest advances in heterologous biosynthesis to produce natural compounds from _Streptomyces_, which include the overexpression/deletion of regulatory genes, promoter replacement strategies, and engineering of ribosomes. On the other hand, many natural secondary metabolites, semi-synthesized or synthesized in the laboratory or by a biotechnological approach, exhibit excellent pharmacodynamics but very poor pharmacokinetic properties. The development of nano delivery systems has been a successful way to overcome the pharmacokinetic limitations of many natural compounds, allowing them to broaden their medicinal application [18], [PERSON] et al. [19] present in this Special Issue a review of the literature on the development of nano formulations involving natural compounds with application in the treatment of cardiovascular diseases, highlighting those with the most significant results for the prevention and treatment of this type of disease, that is, cases involved in clinical studies. As referred to before, invasive species are considered one of the most significant global threats to biodiversity.