1 Introduction

Rutaceae comprises around 2070 species distributed into 154 genera with a nearly cosmopolitan distribution (Kubitzki et al. 2011; Christenhusz and Bing 2016). Species of the family occur as trees, shrubs and herbs found predominantly in tropical and subtropical habitats (Morton and Telmer 2014). The family has been economically important primarily for edible fruits, especially Citrus L., timbers from Balfourodendron Mello ex Oliv. and Zanthoxylum L., bitter beverages employed to treat fevers (Angostura Roem. & Schult and Galipea Aubl.) and drugs (Pilocarpus Vahl. species) (Groppo et al. 2012).

For over 100 years, pilocarpine, an alkaloid isolated from the Brazilian species Pilocarpus microphyllus Stapf ex Wardlew., has been used as a drug to treat glaucoma. Pilocarpine has cholinergic properties and can stimulate the parasympathetic system, acting in the sudoriferous and salivary glands (Debnath et al. 2018; Adejoke et al. 2019). A plethora of biological activities have been described for extracts and compounds isolated from Rutaceae species (Li et al. 2017; Forkuo et al. 2020; Passos et al. 2021; Dos Santos et al. 2021; Mbaveng et al. 2021; Ombito et al. 2021). Undoubtedly, the biosynthetic machinery of the family is highly diversified, producing several classes of secondary metabolites. Consequently, thousands of natural products such as alkaloids, coumarins, flavonoids, limonoids and other terpenoids have been identified from Rutaceae species (Epifano et al. 2015; Adamska-Szewczyk et al. 2016; Abotaleb et al. 2020; Coimbra et al. 2020; Wei et al. 2020; Ombito et al. 2021).

The Rutaceae includes two subfamilies (Cneoroideae and Rutoideae), six main clades, the tribes Aurantieae, Diosmeae, Galipeeae, Ruteae, Zanthoxyleae and the AAMAO clade. Of these, the tribe Galipeeae comprises two subtribes Galipeinae and Pilocarpinae, with around 218 species and 25 genera (Cole and Groppo 2020).

Pilocarpinae has Neotropical distribution and currently includes six genera Balfourodendron Mello ex Oliv., Esenbeckia Kunth, Helietta Tul., Metrodorea A.St.-Hil., Pilocarpus Vahl and Raulinoa R.S.Cowan (Cole and Groppo 2020). Phytochemical studies on species of Pilocarpinae include a range of compounds, mainly composed of alkaloids (Santos and Moreno 2004; Gómez-Calvario et al. 2019) and coumarins (Santos and Moreno 2004; Ferreira et al. 2010; Madeiro et al. 2017).

Esenbeckia comprises 28 species, distributed from Mexico through Argentina, and in the West Indies (Kaastra 1982; Pirani 1999; Dias et al. 2013). The genus is centered in Brazil and Mexico, where 15 species occur in each country (Villaseñor, 2016; Pirani and Groppo 2020). In the monograph of Pilocarpinae, Kaastra (1982) divided Esenbeckia into three subgenera: Esenbeckia, Lateriflorens, and Oppositifolia according to leaves' features and side branchlets and position of inflorescences. Additionally, Esenbeckia subg. Esenbeckia was subdivided into two sections, distinguished by the presence and absence of basal appendage on the staminal filaments as, respectively, Esenbeckia subg. Esenbeckia sect. Pachypetalae and Esenbeckia subg. Esenbeckia sect. Esenbeckia (Kaastra 1982).

In folk medicine, some species of Esenbeckia are traditionally used to treat illness. Esenbeckia yaaxhokob Lundell is known as “tankas-ché” by communities along the Peninsula of Yucatan (Mexico), and the aerial parts are used to treat gastrointestinal disorders (Mata et al. 1998). Similarly, Esenbeckia alata (Triana) Triana & Planch., known as “loro” on the Colombian Atlantic coast, is used as an insecticide and antipyretic (García-Beltrán and Cuca-Suárez 2003). Finally, in the Southwest of Brazil, the bark of Esenbeckia febrifuga (A.St.-Hil.) A.Juss. ex Mart. is considered a medicine for fever and a tonic (Brandão et al. 2012; Cosenza et al. 2019).

Due to the traditional uses and pharmacological activities of Esenbeckia species and the broad diversity of compounds identified from the genus to date, this review surveys the Esenbeckia species' metabolites and associated biological activities, highlighting the importance of this genus as a source of bioactive natural products. Additionally, the meaning of these metabolites for taxonomic purposes is evaluated here, verifying whether they are useful as chemophenetic characters to corroborate the infrageneric taxa currently recognized in Esenbeckia.

2 Compounds identified from Esenbeckia species

Phytochemical and biological activity studies were searched into SciFinder using as keyword Esenbeckia. All papers published in English, Portuguese and Spanish and the abstracts of works written in other languages were compiled until April 2021. To date, chemical constituents isolated or identified from barks, leaves, roots, stems, woods and volatile oils of Esenbeckia species were described. The phytochemical profile of the Esenbeckia genus furnished 180 compounds, divided into alkaloids and amides (1–52; Table 1 and Figs. 1, 2, 3), phenolic compounds (53–115, Table 2 and Figs. 4, 5, 6, 7), steroids & terpenoids (116–174, Table 3 and Figs. 8, 9, 10) and long-chain compounds (175–180, Table 4 and Fig. 11). Authors of species names are presented in Table 5.

Table 1 Alkaloids and amides identified into Esenbeckia species
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Fig. 1
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Acridone (1–3), furoquinoline (4–13) and furoquinolone (14) alkaloids found into Esenbeckia species

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Fig. 2
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Indole (15–27), β-indolopyridoquinazoline (28–30) alkaloids identified from Esenbeckia species

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Fig. 3
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Protoalkaloid (31), pyranoquinolinones (32–34), quinolines (35), quinolinones (36–48) alkaloids and amides (49–52) identified of Esenbeckia species

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Table 2 Phenolic derivatives identified from Esenbeckia species
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Fig. 4
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Chromanone (53) and cinnamic acid derivatives (54–56) identified from Esenbeckia species

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Table 3 Steroids and terpenoids isolated from Esenbeckia species
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Table 4 Long-chain compounds identified from Esenbeckia spp.
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Table 5 Compounds identified in Esenbeckia species; subgenera and sections proposed by Kaastra (1982) are indicated for each species
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Alkaloids –

Esenbeckia is a rich source of nitrogenous natural products providing compounds (1–52, Table 1 and Figs. 1, 2, 3) belonging to nine distinct groups: acridone, furanoquinoline, furanoquinolone, indole, β-indolopyridoquinazoline alkaloids, protoalkaloids, pyranoquinolinone, quinoline and quinolinone alkaloids. Also, amides were identified in three species, E. alata, E. almawillia Kaastra and E. leiocarpa Engl.

Despite the description of three acridone alkaloids, only compound 1 was found in more than one species. Similarly, indole and β-indolopyridoquinazoline alkaloids were identified strictly in E. grandiflora Mart. and E. leiocarpa (Monache et al. 1990, 1991; Januário et al. 2009). Otherwise, furanoquinoline and quinoline alkaloids occur in several species of Esenbeckia, and the compounds flindersiamine (8), kokusaginine (10) and skimmianine (12) are ubiquitously distributed among the species. Compounds with quinoline rings have been explored for drug development (Matada et al. 2021).

Phenolic derivatives –

Esenbeckia species provided 62 phenolic derivatives (53–115, Table 2 and Figs. 4, 5, 6 and 7), distributed among the following natural products classes: chromanone, cinnamic acid derivatives, coumarins, flavonoids, lignoids, phenylpropanoids, simple phenolics and phloroglucinols. Although cinnamic acid derivatives encompass one of the most diverse classes of phenolic compounds (El-Seedi et al. 2012), only three compounds (54–56, Fig. 4) were identified from Esenbeckia species (Monache et al. 1990; Guilhon et al. 1994). Similarly, only five lignoids (106–110, Fig. 7) were identified from E. alata, E. leiocarpa, and E. yaaxhokob (Monache et al. 1990; Mata et al.1998; Suárez and Barrera 2007).

Coumarins are widely distributed in the plant kingdom and this natural product class has been described in several species of Apiaceae, Asteraceae and Rutaceae (Borges et al. 2005). Indeed, coumarins are the largest group among phenolic compounds of Esenbeckia providing 29 constituents (57–86, Fig. 5). A remarkable characteristic of these compounds is the presence of prenyl moieties at the C-6 position. Consequently, furanocoumarins are often identified in the genus instead of simple and pyranocoumarins. Additional prenyl groups are found at C-7 and C-8 positions. Coumarins were described in E. alata, E. almawillia, E. febrifuga, E. flava Brandegee, E. hartmani B.L.Rob. & Fernald, E. hieronymi Engl, E. pumila Pohl and E. stephanii Ramos (Table 2).

Fig. 5
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Simple coumarins (57–59), furanocoumarins (64–85) and pyranocoumarin (86) described from Esenbeckia species

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So far, flavonoids were described exclusively from leaves and roots of E. almawiillia, E. berlandieri Baill, E. grandiflora, E. pumila, E. yaaxhokob. Five groups of flavonoids, i.e., chalcones, catechins, flavanones, flavones and flavanols were identified in the Esenbeckia species (87–105, Fig. 6). Flavonoids within the genus occur either as aglycons and glycosides, with hydroxy, methoxy or glycosyl substitution. Also, 8-prenylated flavanones were identified in E. berlandieri (Table 2; Cano et al. 2006).

Fig. 6
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Catechin (87), chalcones (88–92), flavanones (93–100), flavones (101–102) and flavonols (103–105) identified of Esenbeckia species

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Steroids and terpenoids –

Steroids and several classes of terpenoids such as polyprenols, triterpenoids, limonoids, sesquiterpenoids and monoterpenoids were identified in Esenbeckia species.

Steroids (116–120, Fig. 8) were identified into E. alata, E. belizensis Lundell, E. conspecta (Kaastra) Ramos, E. grandiflora, E. hieronymi, E. leiocarpa, E. litoralis Donn.Sm., E. nesiotica Standl., E. ovata Brandegee, E. stephanii and E. yaaxhokob. However, polyprenols (121–123, Fig. 8) were described only for E. belizensis, E. litoralis, E. neositica and E. yaaxhokob.

Fig. 7
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Lignoids (106–110), phenylpropanoid and simple phenolic (111–112) and phloroglucinols (113–115) described from Esenbeckia species

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Fig. 8
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Steroids (116–120) and polyprenols (121–123) identified from Esenbeckia species

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Triterpenoids (124–140, Fig. 9) belonging to pentacyclic and tetracyclic skeletons were identified into E. alata, E. belizensis, E. grandiflora, E. hartmanii, E. litoralis, E. nesiotica, E. ovata, E. stephanii and E. yaaxhokob. Also, highly oxygenated tetranortriterpenoids, known as limonoids, were described into E. berlandieri, E. febrifuga, E. hartmanii and E. litoralis. Limonoids are restricted to the order Rutales, and these compounds are frequently described in Meliaceae and Rutaceae (Rios and Aguilar-Guadarrama 2002; Roy and Saraf 2006). Limonoids are biosynthesized through oxidative degradation of C-17 side chain of tetracyclic skeletons, such as euphane or tirucallane, which leads to the loss of four carbon atoms as well as the formation of β-oriented furan ring. Additional oxidation and skeletal rearrangements provide structural modifications on the limonoid skeleton, which occur primarily in Meliaceae. Therefore, Meliaceae exploit different biogenetic pathways, leading to more diverse limonoids than in Rutaceae (Da Silva et al., 2021). Nevertheless, limonoids frequently found in Citrus (Rutaceae) have modifications on A and B rings (Roy and Saraf 2006; Tundis et al., 2014), such as Limonin (138) and its derivatives (139 and 140).

Fig. 9
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Triterpenoids (124–137) and limonoids (138–140) identified from Esenbeckia species

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Sesquiterpenoids (141–169, Fig. 10) and monoterpenoids (170–174, Fig. 10) are present in essential oils, primarily studied in E. almawillia. Within Esenbeckia, 32 components were described in two studies of volatile oils; in E. almawillia oils are composed of terpenes and one alkaloid (Barros-Filho et al. 2004), while in E. yaaxhokob they are mainly composed of ketones (Mata et al. 1998). The extractions from barks, leaves, roots and wood of E. almawillia show different compositions within the aerial parts. Many components were found in leaves, whose oils were mainly composed of mono and sesquiterpenes in these aerial parts. Also, extracting essential oil from different parts provided major components such as safrole (112; 60.9–49.17% in barks), selin-11-en-4α-ol (164; 32% in roots), β-caryophyllene (145; 33.75% in leaves) and the alkaloid 3,3-diisopentenyl-N-methyl-2,4-quinoldione (36; 75.28% in woods) (Barros-Filho et al. 2004). Moreover, three other sesquiterpenes, caryophyllene β-oxide (146), clovandiol (148) and spathulenol (166) were identified in leaves of additional species (E. almawillia, E. belizensis, E. conspecta, E. hieronymi, E. litoralis, E. nesiotica, E. ovata, E. stephanii and E. yaaxhokob).

Fig. 10
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Sesquiterpenoids (141–169) and monoterpenoids (170–174) identified from Esenbeckia species

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3 Biological activities of extracts and compounds of Esenbeckia species

Antimicrobial activity –

Two species of Esenbeckia were studied for antimicrobial activity. E. alata and E. yaaxhokob were evaluated against gram-positive and gram-negative bacteria. Crude acetone extract of E. yaaxhokob inhibits the growth of Staphyloccocus aureus Rosenbach and S. faecalis Andrewes and Horder (Aguilar-Guadarrama and Rios 2004), while hydroethanolic extract from E. alata showed low activity in Micrococcous luteus (Schroeter) Cohn assay (García-Beltrán and Cuca-Suárez 2003). Both extracts were fractionated by a bioactive-guided approach. Phytochemical study of E. yaaxhokob yielded the compounds flindersiamine (8), geranyl-N-dimethylallylanthranilate (31) and, spathulenol (166). Compounds 31 and 166 showed minimal inhibitory concentration at 200 µg mL−1 (MIC = 200 µg mL−1) against S. aureus. Also, compound 8 was active against S. aureus (50 µg mL−1) and S. faecalis (100 µg mL−1) (Aguilar-Guadarrama and Rios 2004). From E. alata four compounds were identified including pellitorine (51), 5-hydroxy-2-methylchromanone (53), asarinin (106) and β-sitosterol (117). However, only asarinin showed promising activity against Bacillus subtilis (Ehrenberg) Cohn, Klebsiella pneumoniae (Schroeter) Trevisan and Pseudomonas aeruginosa (Schroeter) Migula (García-Beltrán and Cuca-Suárez 2003).

Cytotoxic activity –

Bioactive-guided studies by MTT assay using three Esenbeckia species evaluated alkaloids (Nunes et al. 2005b; Álvarez-Caballero et al. 2019), triterpenoids (Victor et al. 2017) and synthetic derivatives (Nunes et al. 2005b; Victor et al. 2017) against different tumor cell lines. These studies highlight structure-relationships of Esenbeckia compounds to enhance cytotoxic activities.

Fig. 11
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Fatty acids (176 and 177) and ketones (178–180) identified from Esenbeckia species

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Methanol extract from roots and woods of E. almawillia and its fractions were tested against five tumor cells lines (HL-60 and CEM, human leukemia, B-16 murine melanoma, HCT-8 human colon and MCF-7 human breast). Antitumoral activity was inversely proportional to the polarity of the solvent used in the extraction procedure. Therefore, the most active extract was obtained using hexane as solvent. From this fraction, 3,3-diisopentenyl-N-methyl-2,4-quinoldione (36) was isolated as a primary compound (Nunes et al. 2005b). Although the activity of 36 was tested in all cell lineages, the results demonstrated other non-identified compounds responsible for good activity in the hexane fraction. Also, several modifications in the alkaloid structure leading to O-acyl, O-alkyl and isoprenyl derivatives were obtained, enhancing the activity from the isolated alkaloid and verify structure–activity relationships. Through this study, it was possible to correlate the increase in antitumoral activity with the presence of carbonyl and isoprenyl groups in the structure (Nunes et al. 2005b).

Similarly, structure-relationship studies were performed with α- and β-amyrin derivatives isolated from E. grandiflora. Both compounds were esterified and subsequently treated with amines affording amino acetyl derivatives. These compounds were evaluated by three human tumor cell lines (HCT-116, colon; HL-60, leukemia; and PC-3, prostate) using MTT assay. This study concluded that diethylamine and imidazole derivatives exhibit higher cytotoxic activity, mainly against HL-60 cell line. Additionally, the alkyl chain in dimethylamine and the second coordination atom in the imidazole ring were essential features for this activity (Victor et al. 2017).

Also, the cytotoxic activity of E. alata was evaluated in several tumor cell lines (U251, central nervous system, PC-3 prostate, HCT-15 colon, MCF-7 breast, SKLU-1 lung and K562 myeloid leukemia). The ethanol extract of E. alata at a concentration of 50 µg mL−1 shows 60% activity against K562, PC-3, MCF-7 and SKLU-1 cell lines. The most expressive activity was observed on K562 (97%), indicating a good selectivity of the extract. This pattern was also found for flindersiamine (8) and kokusaginine (10) (86–96% against K562). Comparing both furanoquinoline alkaloids, 10 exhibited higher activity in all tested tumor cell lines, except SKLU-1. Both furanoquinoline alkaloids demonstrated a positive interaction profile with UBA-5 (ubiquitin-activating enzyme 5), as well as binding modes to E1 inhibitor, indicating that studies with furanoquinoline alkaloids are promising for antitumoral therapy development (Álvarez-Caballero et al. 2019).

Leishmanicidal, antiplasmodial and larvicidal activities –

Compounds of E. febrifuga and E. grandifolia furnished positive results as natural treatments against vector-borne diseases such as malaria, dengue, yellow fever, leishmaniasis and Chagas disease.

Esenbeckia febrifuga was a source of compounds against Leishmania major and two strains of Plasmodium falciparum Welch (sensitive to chloroquine, CQS and resistant to chloroquine, CQR). The ethanol extract of E. febrifuga showed activity against CQS and CQR strains IC50 = 21.0 ± 1.4 and 15.5 ± 0.7 µM, respectively; however arborinine (3) and rutaevin (140) were considered inactive. On the other hand, γ-fagarine (7) and skimmianine (13) exhibited moderate activity, indicating a synergistic effect contributing to observed activity in the extract (Dolabela et al. 2008). Also, auraptene (59), isolated from E. febrifuga, significantly inhibits promastigote forms of Leishmania major Yakimoff & Schokhor (LD = 30 µM). The molecular configuration of 59 showed that planarity and intermolecular interactions were similar to other inhibitors of Leishmania (Napolitano et al. 2004).

Coumarins isolated from E. grandifolia were good agents against Aedes aegypti L. larvae. Mixtures of isopimpinellin (77) and pimpinellin (80) as well as 80 and swietenocoumarin B (84) were also effective against larvae (LC50 = 45.77 and 62.23 ppm, respectively). Both mixtures may represent an alternative source to A. aegypti control (Oliveira et al. 2005).

Anti-inflammatory activity –

Esenbeckia leiocarpa has been pointed out as a promisor anti-inflammatory agent. Hydroethanolic extract showed relevant properties as a mediator in inflammatory response. The extract was able to significantly reduce NO, IL-1β and TNF-α levels and inhibit myeloperoxidase (MPO) and adenosine deaminase (ADA) enzymes involved in activation of neutrophils and mononuclear leukocytes (Liz et al. 2011). Indeed, activation of human polymorphonuclear neutrophils by this extract was proven by actin polymerization, cell events signaling and cleavage of cytoskeletal proteins (Pozzatti et al. 2011), together with induction of neutrophil apoptosis (Liz et al. 2012a). To isolate and test compounds produced by E. leiocarpa, hydroethanolic crude extract was fractionated through an acid-basic extraction, leading to an enriched alkaloid fraction, treated with ethyl ether and yielding soluble and insoluble subfractions (Liz et al. 2011, 2012b, 2013; Pozzatti et al. 2011). The soluble subfraction was the most active and furnished dihydrocorynantheol (22) and β-sitosterol (117) (Liz et al. 2011, 2013; Pozzatti et al. 2011). Both compounds inhibited inflammation induced by carageen (Liz et al. 2011). However, in vitro and in vivo assays demonstrated a pleiotropic effect of compound 117 in a dose-dependent manner and showing anti-inflammatory effectiveness only in higher doses (Liz et al. 2013).

Allelopathic and antifeedant activities –

Essential oils extracted from aerial parts of E. yaaxhokob inhibited radicle growth of Lycopersicum esculentum Mill. (89.4%, 1000 µg mL−1) and germination of Echonochloa crusgalli (L.) P. Beauv. (88.3%, 1000 µg mL−1), Lactuca sativa L. (86.5%, 1000 µg mL−1) and Lycopersicum esculentum (82.5%, 1000 µg mL−1). This extract was mainly composed of 2-tridecanone (179; 84%), which also exhibit high phytotoxicity (Mata et al. 1998). Similarly, imperatorin (75) was also identified into E. yaaxhokob and was considered an allelopathic agent and phytogrowth inhibitor. These characteristics are shown through ATP synthesis inhibition (IC50 = 71.5 ± 1.3 µM) and as an uncoupling agent, activating Mg2+ ATPase by 614% (Mata et al. 1998).

Antifeedant activity was described into two quinoline alkaloids isolated from E. leiocarpa. Leiokinine B (47) and leptomerine (48) showed antifeedant activity against a pink bollworm Pectinophora gossypiela Saunders (Nakatsu et al. 1990).

Anticholinesterase activity –

Esenbeckia leiocarpa furnished compounds with anticholinesterase activity, which is pointed out as a possible alternative for the treatment of Alzheimer's disease. The alkaloids skimmianine (13) and leiokinine A (46) inhibited acetylcholinesterase (AChE) (IC50 = 0.21 mM). Also, kokusaginine (10; IC50 = 46 µM) and leptomerine (48; IC50 = 2.5 µM) were similar to galantamine and physostigmine, reference drugs to anticholinesterase activity (Cardoso-Lopes et al. 2010).

4 Chemophenetic characters of Esenbeckia species

Compounds identified in Esenbeckia species are distributed in Table 5 according to division into subgenera and sections proposed by Kaastra (1982). The chemical data do not corroborate the taxa below genus level proposed for Esenbeckia, since it is not possible to find compounds that characterize any subgenus or section.

According to the distribution of metabolite classes, E. pumila is an outgroup because it has been under investigated chemically. Only the flavonoid rutin (105) was described for E. pumila.

Alkaloids were widespread in Esenbeckia, however they were not identified into E. berlandieri, E. nesiotica, E. ovata and E. stephanii. Further investigation should be carried out to ensure the absence of alkaloids in these species. Quinolinone alkaloids have previously been suggested as a chemotaxonomic marker of the genus (Barros-Filho et al. 2004). However, these compounds were only identified in E. almawillia, E. flava, E. grandiflora, E. leiocarpa and E pentaphylla (MacFad.) Griseb. Furanoquinolines alkaloids were considered important characters in Esenbeckia (Rios et al. 2002a). These compounds were identified in all alkaloid producers' species. Also, flindersiamine (8), kokusaginine (10) and, skimmianine (13) are widely distributed in Esenbeckia. On the other hand, indole and β-indolopyridoquinazoline alkaloids were identified only of E. leiocarpa and E. grandiflora, respectively. Acridone, pyranoquinoline and quinolinone alkaloids are of restricted occurrence among Esenbeckia species (Table 5). Thus, these alkaloid types could be useful to distinguish groups of species.

Previous works demonstrated that simple and furanocoumarins are widely distributed in Esenbeckia (Rios et al. 2002a; Simpson and Jacobs 2005). Although several coumarins were isolated through phytochemical studies on the genus, E. belizencis, E. flava, E. hartmanii, E. nesiotica, E. pilocarpoides Kunth and E. stephanii there is no description of such compounds. Furanocoumarins were identified in all other studied species, however, simple coumarins were identified only of E. alata, E. conspecta, E. febrifuga, E. grandiflora, E. hieronymi and E. pentaphylla.

Due to restricted occurrence, it has been suggested that once a limonoid is identified in a species, it is highly probable that the whole genus is limonoid-producer (Dreyer 1980). However, to date, limonoids were only identified at E. berlandieri, E. febrifuga, E. flava, E. hartmanii and E. litoralis. This suggests that the limonoids may be restricted to a group (or groups) of Esenbeckia species, but the lack of a phylogeny of the genus prevents any conclusion so far. Additionally, oxidation levels of limonoids correlates well with Rutaceae subfamilies' distribution (Dreyer et al. 1972). Esenbeckia belongs to the Rutoideae subfamily (Cole and Groppo 2020), which is characterized by oxidation at the C-19 methyl group (Dreyer et al. 1972). This oxidation pattern was also observed in limonoids (138–140) identified in Esenbeckia. In general, the limonoids in the Rutaceae do not show the structural diversity and abundance observed in the Meliaceae (Da Silva et al. 2021).

5 Prospects

The review summarized 180 identified compounds and several biological activities described in 19 species of Esenbeckia. Alkaloids, phenolic derivatives, terpenoids and long-chain compounds were the main classes of metabolites extracted from the genus. Some compounds can be used as chemophenetic characters to define groups of species. However, these groups do not agree with the subgenera and sections proposed for Esenbeckia. Moreover, a phylogenetic study of the genus is not available yet. Therefore, these chemophenetic characters should be reevaluated on a phylogenetic framework within Esenbeckia.

Also, the review of compounds in Esenbeckia highlight this genus as a good source of biological activities, primarily due to furanocoumarin, furoquinoline alkaloids and terpenes production. Compounds with quinoline rings are widely studied through several biological activities and have been an essential source for drug development. Also, extracts and fractions of Esenbeckia species are reported for potential activity in controlling against vector-borne diseases and antimicrobial, anti-inflammatory and cytotoxic properties. Undoubtedly, the phytochemical studies of the genus are an opportunity for future discoveries of new natural products, once 20% of compounds described of Esenbeckia are unique structures.