title: The Chemistry and Pharmacology of Citrus Limonoids.
abstract: Citrus limonoids (CLs) are a group of highly oxygenated terpenoid secondary metabolites found mostly in the seeds, fruits and peel tissues of citrus fruits such as lemons, limes, oranges, pumellos, grapefruits, bergamots, and mandarins. Represented by limonin, the aglycones and glycosides of CLs have shown to display numerous pharmacological activities including anticancer, antimicrobial, antioxidant, antidiabetic and insecticidal among others. In this review, the chemistry and pharmacology of CLs are systematically scrutinised through the use of medicinal chemistry tools and structure-activity relationship approach. Synthetic derivatives and other structurally-related limonoids from other sources are include in the analysis. With the focus on literature in the past decade, the chemical classification of CLs, their physico-chemical properties as drugs, their biosynthesis and enzymatic modifications, possible ways of enhancing their biological activities through structural modifications, their ligand efficiency metrics and systematic graphical radar plot analysis to assess their developability as drugs are among those discussed in detail.
authors.affiliation: Department of Chemistry "U. Shiff", University of Florence, Via della Lastruccia 3, Florence 50019, Italy. roberta.gualdani@unifi.it.
authors.forename: Roberta
authors.initials: R
authors.lastname: Gualdani
authors.affiliation: Department of Pharmacy-Drug Sciences, University of Studies of Bari Aldo Moro, Via E. Orabona n. 4, Bari 70126, Italy. mariamaddalena.cavalluzzi@uniba.it.
authors.forename: Maria Maddalena
authors.initials: MM
authors.lastname: Cavalluzzi
authors.affiliation: Department of Pharmacy-Drug Sciences, University of Studies of Bari Aldo Moro, Via E. Orabona n. 4, Bari 70126, Italy. giovanni.lentini@uniba.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Lentini
authors.affiliation: Pharmacognosy Research Laboratories & Herbal Analysis Services, University of Greenwich, Central Avenue, Charham-Maritime, Kent ME4 4TB, UK. s.habtemariam@herbalanalysis.co.uk.
authors.forename: Solomon
authors.initials: S
authors.lastname: Habtemariam
mesh_terms: D002957:Citrus / Q000737:chemistry*; D006801:Humans; D036701:Limonins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D036701:Limonins; D010936:Plant Extracts
keywords: anticancer; antidiabetic; antiinflammatory; antimicrobial; antioxidant; citrus limonoids; developability; insecticidal; lead compound; ligand efficiency metrics; structure-activity relationships; tetranortriterpenoids