# Natural Compounds: A Dynamic Field of Applications
## 2 Contributions  
Several original papers included in this Special Issue involve the search for new antibacterial and antifungal agents, mainly from secondary metabolites, their derivatives and essential oils of different plant species. Essential oils are a mixture of volatile compounds, mainly mono-, di- and sesquiterpenes, with high commercial value and a wide range of applications [19; 40]. _Piper caldense_ (Piperaceae family) is popularly used for the treatment of snakebites, stomach problems and as a sedative [41]. The research presented by [PERSON] et al. [42] shows that essential oils from _P. caldense_ leaf are composed, in major proportions, by sesquiterpenes such as carryophyllene oxide, spathulenol, \(\gamma\)-cadinene and bicyclogermacrene. Although the essential oils do not show antifungal activity against _Candida albicans_, they exhibit a synergistic effect with the antifungaluconazole, which increase their activity when used combined. This modulator effect is not observed at the highest concentration. The ability of essential oils to cause complete inhibition of the hyphae prolongation was also demonstrated, being an effect superior to fuconazole [42], which suggests their application as an adjuvant in antimicrobial formulations. _Helianthus annuus_ (Asteraceae, sunflower) has been used as a traditional medicine to treat a variety of ailments, such as rattlesnake, spider, snake and scorpion bites, fevers [43; 44], food poisoning [45], burning sensation in the vagina and worms in the ears [46]. [PERSON] et al. [47] report the chemical composition and antifungal activity of essential oils from the aerial parts of two cultivars of _H. annuus_, \"Chianti\" and \"Mammoth\", and wild-growing _Helianthus strumosus_. Analysis of these essential oils shows they are qualitatively similar and dominated by monoter, in particular sabinene, \(\alpha\)-pinene, \(\beta\)-pinene and limonene. The antifungal activity of essential oils and their main constituents were evaluated against three opportunistic pathogenic fungal species, _Aspergillus niger_, _Candida albicans_ and _Cryptococcus neoformans_, which mainly affect immunocompromised patients. The essential oils of _H. annus_ \"Chianti\" and \(H\). _strumosus_ are the most active against \(C\). _neoformans_ and the authors consider that the activity is due to both enantiomers of pinene. Carvacrol is a usual essential oils constituent, that exhibits activity against _Penicillium digitatum_, a citrus crop fungal which causes significant economic losses [48], but whose mechanism of action is not completely clarified. Using an innovative approach, metabolomics based on \({}^{1}\)H-NMR analysis, [PERSON] et al. [49] determine the changes introduced into the _P. digitatum_ metabolism and its energetic balance when this fungus is treated with carvacrol. The results show this compound induces ROS production on _P. digitatum_, which mainly disturbs the energy production by a decrease in glycolysis followed by an augmentation in gluconeogenesis involving mainly alanine, aspartate and glutamate metabolism. Phenolic nor-triterpene are described in the literature as antibacterial agents against Gram-positive bacteria [50; 51; 52]. [PERSON] et al. [53] report the antimicrobial activity of five natural phenolic nor-triterpenes, isolated from _Maytenus pleirades_ and _Maytenus canariensis_, and four pristinerin derivatives synthesized. The most active compound was the derivative 6\(\alpha\)-hydroxy-2,3-diacetoxy-pristimerol which is more active than the positive control cephalospor against spore-forming bacteria and _Staphylococcus epidermidis_. A comprehensive structure/activity relationship (SAR) study was performed with the aim of the rational design of antimicrobial agents based on the phenolic nor-triterpene scaffold.