Excelxylin A: a new seco A-ring tirucallane triterpenoid from the stem bark of Dysoxylum excelsum.

A new seco-A tirucallane triterpenoid named excelxylin A (1), along with two known seco-A triterpenoids (2-3), were isolated from the n-hexane extract of Dysoxylum excelsum (Spreng.) Blume ex G.Don stem bark. The structure and stereochemistry configuration of compounds 1-3 was established by NMR, IR, and HR-ESI-MS spectroscopic data analyses and comparison of their NMR data with literatures. The compounds exhibited the carbon framework for seco-A ring tirucallane triterpenoid, first reported in the Dysoxylum genus. All compounds were tested for their cytotoxicity against human cervical HeLa cells.

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.

Paraxylines A-G: Highly oxygenated preurianin-type limonoids with immunomodulatory TLR4 and cytotoxic activities from the stem bark of Dysoxylum parasiticum.

Seven previously undescribed preurianin-type limonoids, namely paraxylines A-G, and three known analogs were isolated from stem bark of Dysoxylum parasiticum. The structures, including absolute configurations, were established through spectroscopic analyses, quantum chemical calculations using the density functional theory method, as well as the DP4+ algorithm. Paraxylines A-G were identified as the first preurianin-type with full substitution at C, D-rings, leading to the highly oxygenated seco-limonoids skeleton. The secreted alkaline phosphate assay against an engineered human and murine TLR4 of HEK-Blue cells was performed to evaluate the immune regulating effects. Among them, paraxyline B was found to be a remarkable TLR4 agonist whereas two analogs (toonapubesins A and B) were found to antagonise lipopolysaccharide stimulation of the TLR4 pathway. Paraxylines A and C-E acted either as agonists or antagonists depending on the origin of the TLR4 receptor (human or mouse). The effect of these selected compounds on the expression of pro-inflammatory cytokines TNF-α, IL-1α, IL-1ß, and IL-6 of the NF-κB signaling pathway were examined in macrophage cell lines, revealing dose-dependent effects. Additionally, paraxylines A, C, D, and G also presented modest cytotoxic activity against MCF-7 and HeLa cell lines with IC50 values ranging from 23.1 to 43.5 µM.

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.

New steroid produced by Periconia pseudobyssoides K5 isolated from Toona sureni (Meliaceae) and its heme polymerization inhibition activity.

A new ergostane-type steroid named (22E)-3α,6α,9α-ergosta-7,22-diene-3,6,9-triol (1), along with six known steroids 5α,8α-epidioxy-24-ethyl-cholest-6-en-3ß-ol (2), ergosterol-5,8-peroxide (3), cerevisterol (4), isocyathisterol (5), 6ß-hydroxystigmast-4-en-3-one (6), 6ß-hydroxy-4-campesten-3-one (7), were isolated from the fermented unpolished rice media by Periconia pseudobyssoides K5 (Periconiaceae), an endophytic fungus from medicinal plant Toona sureni (Meliaceae). The fermentation takes at 28 ± 2 °C for 30 days. The structure of new steroid (1) was elucidated by extensive spectroscopic measurements (IR, HR-ESI-TOFMS, and 1D and 2D NMR) analyses. The isolated compounds (1-7) were evaluated for heme polymerization inhibition assay (HPIA). The IC50 HPIA value of 1 is 8.24 ± 0.03 mg/ml.

Dysoticans F-H: three unprecedented dimeric cadinanes from Dysoxylum parasiticum (Osbeck) Kosterm. stem bark.

An asymmetrical true-dimeric cadinane via ketonic bridge [C-15/C-3'], dysotican F (1), two symmetrical pseudo-cadinane dimers through an O-ether linkage [C-3/C-3'], dysoticans G (2) and H (3), as well as three known sesquiterpenoids 4-6 were obtained from the stem bark of Dysoxylum parasiticum (Osbeck) Kosterm. (Meliaceae). Their structures were determined by spectroscopic and quantum chemical calculations of 13C NMR shifts using a GIAO method and electronic circular dichroism (ECD) using a TDDFT method. A possible biogenetic pathway for 1-3 beginning from the known compounds (i-ii) was proposed. Cytotoxic evaluation showed that 2 as a new lead compound is the most potent against the MCF-7 and HeLa cell lines with IC50 values of 12.07 ± 0.17 µM and 9.29 ± 0.33 µM, while 1 has moderate inhibition with IC50 values of 31.59 ± 0.34 µM and 27.93 ± 0.25 µM. Furthermore, 3 is a selective inhibitor against the HeLa cell growth with an IC50 value of 39.72 ± 0.18 µM. A brief structure-activity relationship analysis of all isolated compounds 1-6 was also provided, including comparison with the coexisting molecules in the previous report.

New Triterpenoids from Lansium domesticum Corr. cv kokossan and Their Cytotoxic Activity.

Lansium domesticum Corr. is a member of the Meliaceae family that is widely spread in tropical and subtropical region of Asia and America. Traditionally, the fruit of this plant has been consumed because of its sweet taste. However, the fruit peels and the seeds of this plant have been rarely utilized. The previous chemical investigation of this plant showed the presence of secondary metabolites with many biological activities, including cytotoxic triterpenoid. Triterpenoids is a class of secondary metabolites which contain thirty carbon atoms in the main skeleton. The high modification of this type of compound, including the ring opening, highly oxygenated carbons, and the degradation of its carbon chain to give the nor-triterpenoid structure, is responsible for its cytotoxic activity. In this paper, we isolated and elucidated the chemical structure of two new onoceranoid triterpenes, kokosanolides E (1) and F (2), from the fruit peels of L. domesticum Corr., along with a new tetranortriterpenoid, kokosanolide G (3), from the seeds of L. domesticum Corr. The structural determination of compounds 1-3 was undertaken through FTIR spectroscopic analysis, 1D and 2D NMR, mass spectrometry, as well as through a comparison of the chemical shifts of the partial structures of compounds 1-3 with the literature data. The cytotoxic properties of compounds 1-3 were tested against MCF-7 breast cancer cells using the MTT assay. Moderate activity was shown by compounds 1 and 3, with IC50 values of 45.90 and 18.41 µg/mL, respectively, while compound 2 showed no activity (IC50 168.20 µg/mL). For the onoceranoid-type triterpene, the high symmetrical structure of compound 1 is presumably the reason for its better cytotoxic activity compared with that of compound 2. Compound 3 showed moderate activity, mainly because of the presence of the furan ring, which, based on the literature, gives better cytotoxic activity in a tetranortriterpenoid-type structure. The findings of three new triterpenoid compounds from L. domesticum indicate the significant value of this plant as a source of new compounds.

Tirucallane-type triterpenoid from the stem bark of Chisocheton lasiocarpus and its cytotoxic activity against MCF-7 breast cancer cells.

Chisocarpene A (1) is a new tirucallane-type triterpenoid together with odoratone (2) and 24-methylenecycloartanol (3), isolated from the stem bark of Chisocheton lasiocarpus. The chemical structures of compounds 1-3 were elucidated through a detailed analysis of their spectroscopic data (IR, MS, 1 D, and 2 D NMR). The isolated compounds were evaluated for cytotoxic activity against the MCF-7 breast cancer cell line using a resazurin-based assay. Compound 1 showed the most potent activity (IC50 26.56 ± 1.01 µM) and was two-fold more active than the positive control.

Sesquiterpenoids and sesquiterpenoid dimers from the stem bark of Dysoxylum parasiticum (osbeck) kosterm.

Two undescribed sesquiterpenoids, namely dysoticans A and B, and three undescribed sesquiterpenoid dimers, namely dysoticans C-E, together with six analogs, were isolated from the stem bark of Dysoxylum parasiticum (Osbeck) Kosterm. (Meliaceae), growing in West Java, Indonesia. Their structures were elucidated based on extensive spectroscopic analysis and theoretical simulations of ECD spectra and 13C NMR shifts. Dysoticans A and B possessed undescribed cadinanes with minor modifications, while C and D featured unprecedented pseudo-sesquiterpenoid dimers through O-ether linkages of cadinanes and guaianes, respectively. Dysotican E was also characterized as the true-sesquiterpenoid dimer featuring eudesmane-germacrene hybrid framework from the Meliaceae family. Furthermore, A-C and E showed moderate activities against the human breast cancer MCF-7 and cervical cancer HeLa cell lines with IC50 values ranging from 22.15 to 45.14 µM. D selectively exhibited significant cytotoxicity against the HeLa cell line with an IC50 value of 13.00 ± 0.13 µM.

Triterpenoids from Dysoxylum genus and their biological activities.

This study aims to analyze the ethnobotanical, chemical, and biological activities of triterpenoid compounds isolated from the Dysoxylum genus of the Meliaceae family between 1974 and 2021. The species are mainly distributed in Africa, Asia, and Australia, and used as a traditional medicine to treat various diseases. Triterpenoid was first isolated in 1976 and as tetranortriterpenoid or limonoid, it was named dysobinin. Several studies were conducted for more than 40 years on the plants' stems, bark, and leaves, where approximately 279 triterpenoid compounds from several groups such as dammarane, nortriterpenoid, oleanane, lupane, tirucallane, cyclolanostane, or cycloartane, glabretal, and cycloapoeuphane-types were isolated with some synthetic products. In addition, the hypothetical route of triterpenes biosynthesis from this genus was identified, and tirucallane-type were reported to be 37.6% of the total compounds. The anti-malarial, anti-feedant, antimicrobial, anti-inflammatory, antioxidant, vasodilative effect, anti-viral, cortisone reductase, and cytotoxic activities of the extract were also evaluated. The results showed the necessity of using the triterpenoid compounds from the Dysoxylum genus in traditional medicine and the discovery of new drugs.