New Drugs from Old Natural Compounds: Scarcely Investigated Sesquiterpenes as New Possible Therapeutic Agents

Abstract

Sesquiterpenes are natural products that have been extensively studied for their bioactivities, evidencing their potentiality as useful scaffolds for the development of drugs. Considering the different derivatives, the sesquiterpene lactones have been evaluated, especially on cancer cell and antineoplastic efficacy in in vivo studies. Their bioactivity is strictly related to the presence of the reactive α-methylene-γ-lactone group (αMγL). Nevertheless, several other sesquiterpenes lacking αMγL are known and have been studied for their biological effects and potential usefulness in the development of new drugs. In this review, we focused on several sesquiterpenes that are not presenting the αMγL moiety and may have future potential as scaffold for the development of new drugs, namely the bicyclic compounds belonging to the carotane type (daucanes) that present significant effects as antiproliferative and estrogenic agents. The monocyclic humulane derivatives correlated to zerumbone, and the bicyclic compound beta-caryophyllene and its derivatives that have been considered in the field of cancer and inflammation. It is noteworthy that published studies on sesquiterpenes, reported in this review, focus on pathologies of increasing importance, like estrogen, anti-proliferative, bone loss, immunity deficiency and anti-tumour activities. Some of the natural "old" sesquiterpenes can be considered for their possible role in drug discovery and in counteracting these "new" challenges.

Terpenoids, Cannabimimetic Ligands, beyond the Cannabis Plant

“…These are few very important examples of the beneficial and useful properties of caryophyllene. We agree with Sut and co-workers' point-of-view that some of the considered old molecules, as sesquiterpenes, could possibly play an important role in drug discovery towards new discoveries [99].…”

Tumor-derived lactate induces M2 macrophage polarization via the activation of the ERK/STAT3 signaling pathway in breast cancer

“…Therefore, we predict that suppression of the lactate signaling pathway that induces M2-like macrophages should improve the macrophage phenotype to prevent cancer. Natural compounds are a major source of current chemotherapeutic agents, and the chemotherapeutic and chemopreventive effects of such compounds have been demonstrated both in preclinical and clinical studies [18]. Therefore, identification of candidate compounds with antitumor activity from the natural compound library has an important role in the research and development of new drugs.…”

“…Our present data demonstrated that suppression of the lactate signaling pathway that induces M2-like macrophages should change macrophage functions to prevent cancer proliferation, migration, and angiogenesis. It is believed that natural compounds are a good source of new drugs [18]. Withanolide D (C4b-C5b, C6b-epoxy-1-oxo-,20b, dihydroxy-20S, 22R-witha-2,24-dienolide; C28H38O6, MW 470.6; WithaD) is a steroidal lactone isolated from the leaves and roots of Withania Somnifera [19], which is one of the most reputed Indian medicinal plants and forms the essential constituent of more than 100 traditional medicine formulations [20].…”

Ferutinin Induces Membrane Depolarization, Permeability Transition Pore Formation, and Respiration Uncoupling in Isolated Rat Liver Mitochondria by Stimulation of Ca2+-Permeability

“…There is a strong interest to plant compounds as potential pharmacological agents due to their effectivity, safety and a wide spectrum of biological activities, including anticancer effect (Amin et al 2009;Fulda 2010;Mondal et al 2012;Ouyang et al 2014). Terpenoids are quite promising as chemotherapeutic agents among potential anticancer drugs (Modzelewska et al 2005;Dall' Acqua et al 2011;Safi et al 2016;Suta et al 2017). One of such compounds is ferutinin, a sesquiterpene isolated from plants of Ferula genus (Umbelliferae family).…”