Terpenes

Sesquiterpenes are terpene compounds, containing three isoprene units rearranged in a wide variety of structures. They occur widely in nature, not only in plants but also in fungi and marine environments. Owing to peculiar structures and diverse biological activities, they attracted great attention in pharmaceutical, medicinal chemistry and nutraceutical fields. The present chapter collects novel insights into chemistry, distribution in nature and pharmacological properties of sesquiterpenes, focusing especially on caryophyllane, lactone-type, and eremophilane subgroups, due to the growing pharmacological interest. Novel structures and alternative natural sources to be further investigated and exploited have been highlighted too. Moreover, some issues regarding toxicity risk and bioavailability of sesquiterpenes, which can limit their application in practice, have been discussed.

Cannabis sativa L. has been used for millennia by humans for medicinal, ritual and recreational uses. Commonly known under its dried form (flowers and leaves) as marijuana, this plant produces hundreds of phytomolecules, including phytocannabinoids, terpenes and flavonoids. Over the past decades, it is most abundant and most therapeutically relevant component, (-)-trans-Δ9-tetrahydrocannabinol (Δ9- THC) has generated considerable interest due to its various therapeutic properties. Most of them result from the interaction with two G-protein coupled receptors named cannabinoid receptors (CB1 and CB2). This chapter gives a broad overview of the main structural investigations performed on the natural scaffold of Δ9-THC in order to modulate the affinity for the cannabinoid receptors and, potentially, its therapeutic properties. The design of several synthetic cannabinoid derivatives will be presented, and their structure-activity relationships will be analysed.

Aromatic plants have been used since ancient times for their medicinal properties, including potent antimicrobial activity. Strong evidence indicates that plant extracts, in general, and essential oils (EOs), in particular, can act as effective antimicrobial agents against a wide spectrum of pathogenic microorganisms. However, their poor water solubility and stability, as well as their high volatility, make the administration of EOs to achieve the desired therapeutic effects particularly challenging. Therefore, these features severely limit the application of EOs in the pharmaceutical field. In this context, nanotechnology-based strategies for developing nano-scaled carriers for the efficient delivery of EOs might offer potential solutions. In particular, considering the lipophilic nature of EOs, lipid-based nanocarriers represent the most suitable vehicles for the effective encapsulation and delivery of EOs. This chapter provides an overview of the different chemical compositions due to various endogenous and/or exogenous factors of a selection of oils and the most recent lipid-based encapsulation strategies to enhance their antimicrobial activity and promote their pharmaceutical application.

Malaria is a vector-borne tropical disease caused by protozoans belonging to the genus Plasmodium, which has been scourging mankind for hundreds of millions of years. Despite the masterful progress in preventing disease transmission and reducing morbidity and fatal outcomes, malaria is on the rise again. Global concerns are focused on the spread of resistance to current drugs in the management of severe or ultimately lethal P. falciparum infection. To fully exploit the potential of existing agents and overcome their critical drawbacks, novel synthetic and formulation approaches have been explored. In this field, the clinical value of the natural drug artemisinin (ART) and its derivatives have been firmly established, and ART combination therapies (ACTs) have been recommended as first-line treatment against infection caused by chloroquine-resistant (CQR) P. falciparum strains. Over time, however, ART treatment options have become inadequate, and strict demand for new and effective agents has emerged. In this chapter, the medicinal chemistry aspects of artemisinins will be discussed, covering their unique mode of action and their structural features in relation to stability, pharmacokinetic profile, and antiplasmodial activity. Beyond ACT strategies, significant classes of compounds obtained through both ART covalent bitherapy and dimerization approaches will be presented as well. Furthermore, a special section will focus on the most recent endoperoxide-based synthetic antimalarials as new powerful and cost-effective alternatives to the “golden drug”. It is expected that reported results will provide a strong incentive for further studies, and that unceasing research efforts will succeed in reaching the eventual eradication of this endemic plague.