Toonanoronoids A-E, five new limonoids from Toona ciliata var. yunnanensis.

Five new B-seco-limonoids, namely toonanoronoids A-E (1-5), in conjunction with three previously reported compounds, were isolated from the EtOAc extract of the twigs and leaves of Toona ciliata var. yunnanensis. Their structures were elucidated through comprehensive spectroscopic and X-ray crystallographic analysis. The cytotoxic activities of new compounds against five human tumor cell lines (HL-60, SMMC-7721, A549, MCF-7, and SW480) were screened, Compounds 4 and 5 exerted inhibition toward two tumor cell lines (HL-60, SW-480) with IC50 values between 1.7 and 5.9 µM.

Alliaxylines A-E: five new mexicanolides from the stem barks of Dysoxylum alliaceum (Blume) Blume ex A.Juss.

A total of five new mexicanolides (1-5), namely alliaxylines A-E, together with two known limonoids 6 and 7, were isolated and identified from Dysoxylum alliaceum (Blume) Blume ex. A.Juss. (Meliaceae). The structures of these compounds were elucidated based on extensive spectroscopic analyses, including HR-ESI-MS, UV, IR, 1D, and 2D NMR, as well as theoretical stimulation of NMR shifts with the DP4 + algorithm. Consequently, this study aimed to examine cytotoxic activities of these compounds against MCF-7 and A549 cell lines. The results implied that compound 2 was the most potent against the two tested cells, with IC50 values of 34.95 ± 0.21 and 44.39 ± 1.03 µM.

Steroids from the Meliaceae family and their biological activities.

Steroids are farnesyl diphosphate-derived triterpene derivatives widely distributed in Meliaceae plants that can have several health benefits due to their biological activities. This literature survey on chemical and pharmacological studies of steroids from the Meliaceae plants indicates that 157 distinct steroids classified into six subclasses including (in decreasing number): pregnane-, stigmastane-, ergostane-, cholestane-, androstane- and ecdysterone-type steroids have been reported from a total of 49 plant species. This review aims to provide a reference document compiling information about the occurrence, chemistry and biological activities of meliaceous steroids for the period from 1988 to July 2023. In particular, generalities about the chemistry of steroids with unusual skeletons and underlying biosynthetic pathways are highlighted. In addition, some structural relationships between different compound types and their biological activities are presented. The information used during the writing of this paper was collected from the online libraries PubMed, Google Scholar and Scifinder using the keywords steroids and Meliaceae with no language restriction. This review points out new avenues for further investigations of steroids from plants of the Meliaceae family.

Characterization of four new cycloartane triterpenoids from Swietenia macrophylla and their angiotensin-I-converting enzyme inhibitory activity.

Angiotensin I-converting enzyme (ACE) inhibition is currently a common method for the treatment and control of hypertension. In this study, four new (1-4) and one known (5) cycloartane triterpenoids were isolated from the leaves of Swietenia macrophylla by chromatographic techniques and identified by their spectroscopic data and a comprehensive comparison of published data. The triterpenoids were evaluated for their ACE inhibitory potential using in vitro inhibition assays and in silico methods. The inhibition assay and enzyme kinetics results showed that the most active triterpenoid, compound 4, inhibited ACE in a mixed-type manner with an IC50 value of 57.7 ± 6.07 µM. Computer simulations revealed that compound 4 reduces the catalytic efficiency of ACE by competitive insertion into the active pocket blocking the substrate, and the binding activity occurs mainly through hydrogen bonds and hydrophobic interactions. The study showed that S. macrophylla can be a source of bioactive material and the ACE inhibitory triterpenoid could be a potential antihypertensive agent.

Guarea microcarpa C. DC. extract inhibits NLRP3 inflammasome by suppressing its ATPase activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Guarea genus comprises tropical and subtropical terrestrial herbs inhabiting Central and South America. These plants, including Guarea guidonia (L.) Sleumer, have anti-inflammatory, analgesic, antibacterial, antiviral, and immune-enhancing properties. AIM OF THE STUDY: Although various species of the Guarea genus are known for their medicinal properties, comprehensive data on their anti-inflammatory effects remain limited. Therefore, we investigated the NLRP3 inflammasome-inhibiting effects of the Guarea genus in this study. MATERIALS AND METHODS: To evaluate the anti-inflammatory activities of 18 members of the Guarea genus, we treated NLRP3 inflammasome activators with their extracts in LPS-primed J774A.1 and THP-1 cells. Cell viability was determined by water soluble tetrazolium salt (WST) and cytokine production, protein expression, and nuclear fractionation were determined by western blotting. Reactive oxygen species (ROS) production and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) oligomerization were measured using confocal microscopic analysis. Inflammation-induced zebrafish was used in the in vivo experiments. RESULTS: Among the 18 Guarea members tested, Guarea microcarpa C. DC. extract (GM) exhibited no cytotoxicity and specifically suppressed the activation of the NLRP3 inflammasome, but not of the AIM2 or NLRC4 inflammasomes, by inhibiting the ATPase activity of NLRP3. This was achieved without affecting NF-κB signaling, potassium efflux, or intracellular ROS production, all of which are involved in NLRP3 activation. The reduced ATPase activity of NLRP3 led to decreased ASC oligomerization. Furthermore, GM exhibited anti-inflammatory effects in vivo. Additionally, GM treatment alleviated inflammation at the organismal level in an LPS-induced inflammation model using zebrafish embryos. CONCLUSION: Our results demonstrate the anti-inflammatory effects of GM via suppressing the NLRP3 inflammasome. Therefore, GM can be a potential therapeutic candidate for various inflammatory diseases caused by aberrant NLRP3 inflammasome activation.

Ceramicines U-Z from Chisocheton ceramicus and structure-antimalarial activity relationship study.

Ceramicines are a series of limonoids which were isolated from the barks of Malaysian Chisocheton ceramicus (Meliaceae), and were known to show various biological activity. Six new limonoids, ceramicines U-Z (1-6), with a cyclopentanone[α]phenanthrene ring system with a ß-furyl ring at C-17 were isolated from the barks of C. ceramicus. Their structures were determined on the basis of the 1D and 2D NMR analyses, and their absolute configurations were investigated by CD spectroscopy. Ceramicine W (3) exhibited potent antimalarial activity against Plasmodium falciparum 3D7 strain with IC50 value of 1.2 µM. In addition, the structure-antimalarial activity relationship (SAR) of the ceramicines was investigated to identify substituent patterns that may enhance activity. It appears that ring B and the functional groups in the vicinity of rings B and C are critical for the antimalarial activity of the ceramicines. In particular, bulky ester substituents with equatorial orientation at C-7 and C-12 greatly increase the antimalarial activity.

Erythrocarpines IN, new limonoids from the barks of Chisocheton erythrocarpus and their neuroprotective effects against hydrogen peroxide in NG108-15 cells.

A phytochemical study on the bark of Chisocheton erythrocarpus Hiern (Meliaceae) has led to the isolation of six new phragmalin-type limonoids named erythrocarpines I - N (1-6) along with one known limonoid, erythrocarpine F (7). Their structures were fully characterized by spectroscopic methods. The pre-treatment of NG108-15 cells with 1-5, 7 (2 h) demonstrated low to good protective effects against H2O2 exposure; 1 (83.77% ± 1.84 at 12.5 µM), 2 (69.07 ± 2.01 at 12.5 µM), 3 (80.38 ± 2.1 at 12.5 µM), 4 (62.33 ± 1.95 at 25 µM),5 (58.67 ± 1.85 at 50 µM) and 7 (66.07 ± 2.03 at 12.5 µM). Interestingly, 1 and 3 demonstrated comparable protective effects to positive control epigallocatechin gallate (EGCG) with similar cell viability capacity (≈ 80%), having achieved that at lower concentration (12.5 µM) than EGCG (50 µM). Collectively, the results suggested the promising use of 1 and 3 as potential neuroprotective agents against hydrogen peroxide-induced cytotoxicity in neuronal model.

Triterpenoids from the fruits of Aphanamixis polystachya and their inhibitory activities on nitric oxide production.

Nineteen triterpenoids, including five previously unknown (four triucallane-type derivatives and one highly oxidized A, B-seco limonoids), together with fourteen known triterpenoids, were isolated from the fruits of Aphanamixis polystachya. Their structures were elucidated by extensive spectroscopic analysis. All isolates were evaluated their anti-inflammatory activities. The result showed that all compounds inhibit LPS-induced nitric oxide production in RAW264.7 macrophages with their IC50 value ranging from 95 to 1332 uM, and compound 6 exhibited obvious anti-inflammatory activity comparable to that of the positive control, with IC50 values of 94.96 uM.

Antiplasmodial and Antileishmanial Activities of a New Limonoid and Other Constituents from the Stem Bark of Khaya senegalensis.

Plasmodium falciparum and Leishmania sp. resistance to antiparasitic drugs has become a major concern in malaria and leishmaniasis control. These diseases are public health problems with significant socioeconomic impacts, and mostly affect disadvantaged populations living in remote tropical areas. This challenge emphasizes the need to search for new chemical scaffolds that preferably possess novel modes of action to contribute to antimalarial and antileishmanial research programs. This study aimed to investigate the antimalarial and antileishmanial properties of a methanol extract (KS-MeOH) of the stem bark of the Cameroonian medicinal plant Khaya senegalensis and its isolated compounds. The purification of KS-MeOH led to the isolation of a new ordered limonoid derivative, 21ß-hydroxybourjotinolone A (1a), together with 15 known compounds (1bc-14) using a repeated column chromatography. Compound 1a was obtained in an epimeric mixture of 21α-melianodiol (1b) and 21ß-melianodiol (1c). Structural characterization of the isolated compounds was achieved with HRMS, and 1D- and 2D-NMR analyses. The extracts and compounds were screened using pre-established in vitro methods against synchronized ring stage cultures of the multidrug-resistant Dd2 and chloroquine-sensitive/sulfadoxine-resistant 3D7 strains of Plasmodium falciparum and the promastigote form of Leishmania donovani (1S(MHOM/SD/62/1S). In addition, the samples were tested for cytotoxicity against RAW 264.7 macrophages. Positive controls consisted of artemisinin and chloroquine for P. falciparum, amphotericin B for L. donovani, and podophyllotoxin for cytotoxicity against RAW 264.7 cells. The extract and fractions exhibited moderate to potent antileishmanial activity with 50% inhibitory concentrations (IC50) ranging from 5.99 ± 0.77 to 2.68 ± 0.42 µg/mL, while compounds displayed IC50 values ranging from 81.73 ± 0.12 to 6.43 ± 0.06 µg/mL. They were weakly active against the chloroquine-sensitive/sulfadoxine-resistant Pf3D7 strain but highly potent toward the multidrug-resistant PfDd2 (extracts, IC50 2.50 ± 0.12 to 4.78 ± 0.36 µg/mL; compounds IC50 2.93 ± 0.02 to 50.97 ± 0.37 µg/mL) with selectivity indices greater than 10 (SIDd2 > 10) for the extract and fractions and most of the derived compounds. Of note, the limonoid mixture [21ß-hydroxylbourjotinolone A (1a) + 21α-melianodiol (1b) + 21ß-melianodiol (1c)] exhibited moderate activity against P. falciparum and L. donovani. This novel antiplasmodial and antileishmanial chemical scaffold qualifies as a promising starting point for further medicinal chemistry-driven development of a dually active agent against two major infectious diseases affecting humans in Africa.

Undescribed 2,9-deoxyflavonoids and flavonol-diamide [3+2] adduct from the leaves of Aglaia odorata Lour. Inhibit nitric oxide production.

Phytochemical study on the methanol extract of Aglaia odorata leaves resulted in the isolation of four previously undescribed compounds, including three 2,9-deoxyflavonoids and one flavonol-diamide [3 + 2] adduct, and 13 known compounds. The chemical structures of the four undescribed compounds were elucidated on the basis of their IR, HR-ESI-MS, 1D and 2D NMR, and ECD spectra. The results revealed an unprecedented 2,9-deoxyflavonoid framework, which was confirmed by TD-DFT, ECD, and GIAO 13C-NMR calculations using sorted training set methods. The 17 compounds were examined for their ability to inhibit NO production activity in cultured lipopolysaccharide-activated RAW264.7 cells with aglaodoratas A-C, odorine, and epi-odorine inhibiting NO production, with IC50 values in the range of 16.2-24.3 µM. The other investigated compounds had either weak or no activity.

Sesquiterpenoids from Meliaceae Family and Their Biological Activities.

Sesquiterpenoids, an important class of natural products possessing three isoprene-derived units, are widely distributed across plants and have a variety of biological activities. All sesquiterpenoids are derived from farnesyl pyrophosphate (FPP), a biosynthesis precursor that can form various carbon skeletons. In order to provide a reference for further research and development of these compounds, this review focused on the increasing number of isolated and volatile sesquiterpenoids found to be produced by plants of the Meliaceae family between 1968 and 2023. The related articles were collected from SciFinder, Google Scholar, and PubMed. According to a literature review, several studies were started for more than 55 years on the plant's stem barks, twigs, leaves, flowers, seeds, and pericarps, where approximately 413 sesquiterpenoid compounds from several groups such as eudesmane, aromadendrane, cadinane, guaiane, bisabolane, furanoeremophilane, humulene, germacrane, and oppositane-type were isolated and identified with some minor products. Additionally, the hypothetical route of sesquiterpenoids biosynthesis from this family was identified, and eudesmane-type was reported to be 27% of the total compounds. The antimicrobial, antidiabetic, antioxidant, antiplasmodial, antiviral, and cytotoxic activities of the isolated compounds and major volatile sesquiterpenoids constituent on essential oil were also evaluated. The result showed the fundamental of using the sesquiterpenoid compounds from the Meliaceae family in traditional medicine and the discovery of new drugs.

Triterpenoids from the fruits of Melia toosendan Sieb. et Zucc. with α-glucosidase inhibitory activities.

Four previously unreported tirucallane-type triterpenoids (1-4), together with four known analogues (5-8), were isolated from the fruits of Melia toosendan Sieb. et Zucc. Their planar structures were comprehensively elucidated by detailed analyses of HRESIMS, 1D and 2D NMR spectra data. The relative configurations of 1-4 were determined by NOESY experiments. The comparison of experimental and calculated electronic circular dichroism (ECD) spectra led to the establishment of the absolute configurations of new compounds. All isolated triterpenoids were evaluated for their α-glucosidase inhibitory activities in vitro. Compounds 4 and 5 showed moderate α-glucosidase inhibitory activities with IC50 values of 120.3 ± 5.8 and 104.9 ± 7.1 µM, respectively.

Antimalarial ceramicines Q-T from Chisocheton ceramicus.

Ceramicines are a series of limonoids that were isolated from the bark of Malaysian Chisocheton ceramicus (Meliaceae) and were known to show various biological activity. Four new limonoids, ceramicines Q-T (1-4) were isolated from the barks of C. ceramicus, and their structures were determined on the basis of the 1D and 2D NMR analyses in combination with calculated 13C chemical shift data. Ceramicines Q-T (1-4) were established to be new limonoids with a cyclopentanone[α]phenanthren ring system with a ß-furyl ring at C-17, and without a tetrahydrofuran ring like ceramicine B, which is characteristic of known ceramicines. Ceramicine R (2) exhibited potent antimalarial activity against Plasmodium falciparum 3D7 strain with IC50 value of 2.8 µM.

Bioactive limonoids from Carapa guianensis seeds oil and the sustainable use of its by-products.

Carapa guianensis (Andiroba, Meliaceae) is considered a multipurpose tree. In Brazil, Indigenous people have used it as insect repellent and in the treatment of various diseases. Most biological activities and popular uses are attributed to limonoids, which are highly oxygenated tetranortriterpenoids. More than 300 limonoids have been described in Meliaceae family. Limonoids from Andiroba oil have shown high anti-inflammatory and anti-allergic activities in vivo, by inhibiting platelet activating factors and many inflammatory mediators such as IL-5, IL-1ß and TNF-α. It also reduced T lymphocytes, eosinophils and mast cells. In corroboration with the wide popular use of Andiroba oil, no significant cytotoxicity or genotoxicity in vivo was reported. This oil promotes apoptosis in a gastric cancer cell line (ACP02) at high concentrations, without showing mutagenic effects, and is suggested to increase the body's nonspecific resistance and adaptive capacity to stressors, exhibit some antioxidant activity, and protect against oxidative DNA damages. Recently, new methodologies of toxicological assays have been applied. They include in chemico, in vitro, in silico and ex vivo procedures, and take place to substitute the use of laboratory animals. Andiroba by-products have been used in sustainable oil production processes and as fertilizers and soil conditioners, raw material for soap production, biodegradable surfactants and an alternative natural source of biodegradable polymer in order to reduce environmental impacts. This review reinforces the relevance of Andiroba and highlights its ability to add value to its by-products and to minimize possible risks to the health of the Amazonian population.

Phytochemistry and Biological Activities of Endophytic Fungi from the Meliaceae Family.

Meliaceae plants are found worldwide in tropical or subtropical climates. They are important ethnobotanically as sources of traditional medicine, with 575 species and 51 genera. Previous research found that microorganisms are plant pioneers to produce secondary metabolites with diverse compound structures and bioactivities. Several plants of the Meliaceae family contain secondary metabolites isolated from endophytic fungi. Furthermore, related articles from 2002 to 2022 were collected from SciFinder, Google Scholar, and PubMed. About 276 compounds were isolated from endophytic fungi such as terpenoids, polyketides, lactones, pyrones, quinone, anthraquinones, xanthones, coumarines, isocoumarines, resorcylic acid lactones, cytochalasins, aromatics, ester, quinols, alkaloids, nitro compound, fatty acids, and sugars with bioactivities such as antioxidant, antibacterial, antifungal, anti-influenza, neuroprotective activities, anti-HIV, cytotoxic, allelopathic, anti-inflammatory, antifeedant effects, and BSLT toxicity. Meanwhile, secondary metabolites isolated from endophytic fungi were reported as one of the sources of active compounds for medicinal chemistry. This comprehensive review summarizes the ethnobotanical uses and secondary metabolites derived from Meliaceae endophytic fungi.

Volatiles as Attractants of Mahogany Shoot Borer, Hypsipyla grandella Zeller (Lepidoptera: Pyralidae).

The mahogany shoot borer, Hypsipyla grandella Zeller (Lepidoptera: Pyralidae), is one of the most economically important pests in all American tropical forests because it prevents the establishment of monoculture plantations of the family Meliaceae, such as Spanish cedar, Cedrela odorata L. Various studies have focussed on the bioecological aspects and the chemical and silvicultural control of this pest. However, relatively little is known about the biological interactions between this insect and its host plant. In this study, the shoot borer's behavior and attraction response to cedar host plants was evaluated in field cages. We also identified the volatiles emitted by healthy C. odorata plants that were attractive to H. grandella adults. The attraction to headspace volatiles from cedar plants and a synthetic blend were evaluated in a Y-glass tube olfactometer. We observed that virgin and mated females exhibited low activity at night, frequent movement of the antennae, sporadic flight activity, and short (< 10 s) and long (> 30 s) wing-fanning. Virgin females assumed a calling position, whereas mated females exhibited three periods of oviposition. The results showed that all evaluated categories - virgin females, virgin males, and mated females - were attracted to cedar plants. We identified the following volatile compounds: α-pinene, (E)-ß-ocimene, 2-ethyl-1-hexanol, limonene, nonanal, (E)-4,8-dimethyl-1,3,7-nonatriene, α-copaene, ß-caryophyllene, and germacrene D. A synthetic blend significantly attracted virgin male and mated female shoot borers. Our results suggested that C. odorata volatiles compounds are responsible for the attraction of H. grandella.

Phytochemistry and Biological Activities of Guarea Genus (Meliaceae).

Guarea is one of the largest genera of the American Meliaceae family, consisting of over 69 species which are widely distributed in Mexico, Argentina, and Africa and are used in traditional medicine for several diseases. Previous studies reported that the Guarea species produce secondary metabolites such as sesquiterpenoid, diterpenoid, triterpenoid, limonoid, steroid, and aromatic compounds. The preliminary chemical investigation commenced by isolating the limonoid compound, dihydrogedunin, in 1962; then, 240 compounds were obtained from the isolation and hydrodistillation process. Meanwhile, sesquiterpenoid is a significant compound with 52% of Guarea species. The extract and compounds were evaluated for their anti-inflammation, antimalarial, antiparasitic, antiprotozoal, antiviral, antimicrobial, insecticidal, antioxidant, phosphorylation inhibitor, and cytotoxic biological activities. The Guarea genus has also been reported as one of the sources of active compounds for medicinal chemistry. This review summarizes some descriptions regarding the types of Guarea species, especially ethnobotany and ethnopharmacology, such as the compounds isolated from the part of this genus, various isolation methods, and their bioactivities. The information can be used in further investigations to obtain more bioactive compounds and their reaction mechanisms.

Insecticidal Activities and GC-MS Analysis of the Selected Family Members of Meliaceae Used Traditionally as Insecticides.

The environmental and health risks associated with synthetic pesticides have increased the demand for botanical insecticides as safer and biodegradable alternatives to control insect pests in agriculture. Hence in this study, five Meliaceae species were evaluated for their insecticidal activities against the Spodoptera frugiperda and the Plutella xylostella larvae, as well as their chemical constituents. Repellence, feeding deterrence, and topical application bioassays were employed to evaluate their insecticidal activities. GC-MS analysis was performed to identify chemical compounds present in each plant. The repellence bioassay indicated that Melia azedarach extracts exhibited the highest repellence percentage against S. frugiperda (95%) and P. xylostella (90%). The feeding deterrence bioassay showed that M. azedarach and Trichilia dregeana extracts displayed excellent antifeeding activity against the S. frugiperda (deterrent coefficient, 83.95) and P. xylostella (deterrent coefficient, 112.25), respectively. The topical application bioassay demonstrated that Ekebergia capensis extracts had the highest larval mortality against S. frugiperda (LD50 0.14 mg/kg). Conversely, M. azedarach extracts showed the highest larval mortality against P. xylostella (LD50 0.14 mg/kg). GC-MS analysis revealed that all plant extracts had compounds belonging to the two noteworthy groups (phenols and terpenes), which possess insecticidal properties. Overall, this study lends scientific credence to the folkloric use of Meliaceae species as potential biocontrol agents against insect pests.

Ultra-high performance liquid chromatography Q-Orbitrap MS/MS-based profiling and quantification of limonoids in Meliaceae plants.

Meliaceae plants have been extensively used in agriculture, folklore, and traditional medicine. They are the major storehouses for structurally diverse limonoids (meliacins) possessing various bioactivities like antifeedant, insecticidal, antimicrobial, etc. However accurate detection of these tetranortriterpenes from the vast pool of metabolites in plant tissue extracts or biological sample is a crucial challenge. Though the mass spectrum (MS) provides the molecular mass and the corresponding elemental composition, it cannot be relied precisely. The exact identification of a specific metabolite demands the MS/MS spectrum containing the signature product ions. In the present study, we have developed the UHPLC Q-Orbitrap-based method for identification, quantification, and characterization of limonoids in different plant tissue extracts requiring minimum plant material. Using this method, we carried out the limonoid profiling in different tissue extracts of sixteen Meliaceae plants and the identification of limonoids was performed by comparing the retention time (RT), ESI-( +)-MS spectrum, and HCD-MS/MS of the purified fifteen limonoids used as reference standards. Our results revealed that early intermediates of the limonoid biosynthetic pathway such as azadiradione, epoxyazadiradione, and gedunin occurred more commonly in Meliaceae plants. The MS/MS spectrum library of the fifteen limonoids generated in this study can be utilized for identification of these limonoids in other plant tissue extracts, botanical fertilizers, agrochemical formulations, and bio pesticides.

Chukranoids A-I, isopimarane diterpenoids from Chukrasia velutina.

Bioactivity guided separation of Chukrasia velutina root methanolic extract led to the isolation of nine new isopimarane diterpenoids, chukranoids A-I (1-9). The absolute configuration was then assigned by comparing the experimental CD spectra and the calculated CD spectra. Chukranoids A-I (1-9) showed moderate antimalarial activity against Plasmodium falciparum 3D7 strain. It seems that conjugate system in the isopimarane skeleton may influence their antimalarial activity.