title: 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.
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences University of Padova, Padova, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Sut
authors.affiliation: School of Pharmacy, University of Camerino, Camerino, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Maggi
authors.affiliation: Department of Biology, La Sapienza University, Roma, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Nicoletti
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences University of Padova, Padova, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Baldan
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences University of Padova, Padova, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Dall Acqua
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D001688:Biological Products / Q000737:chemistry* / Q000494:pharmacology; D019610:Cytoprotection / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D012717:Sesquiterpenes / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D012717:Sesquiterpenes
keywords: Alpha-methylen-gamma lactone; Lactone group; antineoplastic; disease; sesquiterpenes; therapeutic
  agents; tumor.