Chemical Structures and Biological Activities of Limonoids from the Genus Swietenia (Meliaceae)

Swietenia is a genus in the plant family Meliaceae. This genus contains seven to eight known species, found in the tropical and subtropical regions of the Americas and West Africa. Thus far, more than 160 limonoids have been isolated from four species of the genus Swietenia. Limonoids are rich in structure type and biological activity, and these compounds are the main active components in the Swietenia species. This paper will give a comprehensive overview of the recent phytochemical and pharmacological research on the terpenes from Swietenia plants and encourage further drug discovery research.

Limonoids, classified as tetranortriterpenoids, are formed by the loss of four terminal carbons from a side chain on an apotirucallane or apoeuphane skeleton with cyclization to form a 17β-furan ring [18]. Limonoids are found mainly as important secondary metabolites in the fruits of Rutaceae and Meliaceae plants. Their extensive biological effects, such as anti-malarial [19], antifeedant [20], insecticidal [21], and antitumor properties [22], have attracted the attention of many researchers.

Mexicanolide-Type Limonoids
A total of 77 mexicanolide-type limonoids, 22-98, have been reported from Swietenia species, and most were isolated from S. mahagoni and S. macrophylla. In a few reports, mexicanolide-type limonoids have also been found in S. humilis, for example, humilin B (88) [38], humilinolides A-H

Compounds
Insect and Antifeedant Activity

Conclusions
Swietenia is a genus in the subfamily mahogany (Meliaceae), which is generally considered to contain 7 to 8 species. Among them, the seeds and bark of S. mahagoni, S. macrophylla and S. humilis are used in folk medicines for the treatment of hypertension, diabetes, malaria, and epilepsy in Indonesia, India and Mexico [2,76,77]. Based on the data available, this paper summarizes five types of limonoids and describes various bioactive activities, such as antifeedant, hypoglycemic, antimicrobial, anti-PAF, anti-inflammatory, antitumor, insecticidal, anti-oxidative and antihyperalgesic. Although most of the limonoids isolated from Swietenia species do not show significant antiproliferative effects against cancer cell lines, some structurally similar limonoids isolated from Melia azedarach exhibit good antitumor activity. The best known compound is toosendanin (165), which strong inhibits multiple tumor cell lines; its IC 50 values were 0.005, 0.009 and 0.0054 µM against HL60, AZ521 and U937, respectively [78,79]. In addition, meliarachin C (166), 12-dehydro-29-exo-neoazedarachin D (167), and 1-O-cinnamoyltrichilinin (168) exhibited IC 50 values ranging from 0.65 to 9.1 µM against HL60 [79]. Erythrocarpine A (169), isolated from Chisocheton erythrocarpus, showed cytotoxicity against P388 murine leukemia cells with IC 50 value of 2.0 µg/mL [80] (Figure 7). Its structure differs from that of seenganolide A (67) only by the presence of a benzoyl ester rather than hydroxy group. Therefore, limonoids from the genus Swietenia still have great potential for biological activity and may be modified structurally to improve their activity.
Molecules 2018, 23, x FOR PEER REVIEW 13 of 17 of a benzoyl ester rather than hydroxy group. Therefore, limonoids from the genus Swietenia still have great potential for biological activity and may be modified structurally to improve their activity. Furthermore, the published research on Swietenia has been focused mostly on the seeds and their limonoid components; however, but other plant parts and other compound types may also have rich pharmacological activities. Therefore, it is extremely urgent to expand the scope of research on Swietenia and discover or develop additional biologically active constituents of this plant genus.  Furthermore, the published research on Swietenia has been focused mostly on the seeds and their limonoid components; however, but other plant parts and other compound types may also have rich pharmacological activities. Therefore, it is extremely urgent to expand the scope of research on Swietenia and discover or develop additional biologically active constituents of this plant genus.