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.

Citrus limon (Lemon) Phenomenon—A Review of the Chemistry, Pharmacological Properties, Applications in the Modern Pharmaceutical, Food, and Cosmetics Industries, and Biotechnological Studies

“…They mainly occur in citrus fruits, including lemons, in which they are found mainly in the seeds, pulp, and peel. There are predominantly two such compounds in C. limon fruits-limonin and nomilin ( Figure 3) [37]. Studies have shown that the concentrations of the compounds of this group are dependent on fruit growth and maturation stages.…”

An Integrated Approach to Mandarin Processing: Food Safety and Nutritional Quality, Consumer Preference, and Nutrient Bioaccessibility

“…Aside from polyphenols, limonoids and adrenergic amines (mainly synephrine) are also found in mandarins (Ye and others ). Limonoids are plant alkaloids, modified triterpene glucoside derivatives occurring in mature citrus fruit tissues and seeds (Gualdani and others ). Significant variation in limonoid content was reported in 9 studied mandarin cultivars, where values ranged from 105 to 1128 μg/g DW (Ye and others ).…”

Development of Fortified Citrus Olive Oils: From Their Production to the Nutraceutical Properties on the Cardiovascular System

“…Limonoids are tetranortriterpenoids found in Citrus seeds, pulp, and peels, known as bitter compounds [51]. According to their polarity, limonoids aglycones occur mostly in Citrus peel, while glycoside forms are most abundant in pulp [19]. All compounds were tentatively identified by comparison of their elution order, UV, full MS, and fragmentation pattern (MS/MS) data (Table 6) with those reported in the literature.…”

“…Thus, compound 3 was tentatively identified as limonexic acid or its constitutional isomer isolimonexic acid [55]. Compounds 5 (tR = 41.7 min) and 7 (tR = 43.2 min) had the same molecular weight 546 u and superimposable fragmentation pathways with ions at m/z 501, 457 and 397 generated by the successive losses of two CO2 molecules and an acetyl group, suggesting 5 and 7 to be two isomer forms of citrusin [19]. Compound 10 (tR = 48.4 min) was revealed as formate adduct [M+HCOO] − at m/z 515, which fragmentation generated a base ion peak at m/z 469 due to the loss of a formic acid, thus was tentatively identified as limonin [14].…”