Tirucallane-type Triterpenoids Research Articles

Meliasanines A–L, tirucallane-type triterpenoids from Melia toosendan with anti-inflammatory properties via NF-κB signaling pathway

Meliasanines A–L, twelve previously unreported tirucallane-type triterpenoids, together with fifteen known ones, have been isolated from the stem bark of Melia toosendan. Their structures and absolute configurations were determined based on HRESIMS, and NMR, combined with calculated ECD and single-crystal X-ray diffraction analyses. Subsequently, all compounds except 10 were evaluated for their inhibitory effect on the production of nitric oxide induced by lipopolysaccharide in RAW264.7 macrophage cells. The results indicated that seven compounds (1, 13, 14, 16, 20, 22, and 23) exhibited significant NO inhibitory effects, with IC50 values ranging from 1.35 to 5.93 μM, which were more effective than the positive control indomethacin (IC50 = 13.18 μM). Moreover, the corresponding results of Western blot analysis revealed that meliasanine A (1) can significantly suppress the protein expression of inducible nitric oxide synthase and cyclooxygenase 2 in a concentration-dependent manner. The mechanism study suggested that meliasanine A exerts an anti-inflammatory effect via the nuclear factor-κB signaling pathway by suppressing phosphorylation of P65 and IκBα.

Four new tirucallane-type triterpenoids from Aphanamixis polystachya

Four new tirucallane-type triterpenoids, polystanins H–K (1–4), were obtained from the stems and leaves of Aphanamixis polystachya. Their structures were elucidated by analysis of the spectroscopic data and comparison with literature data. Compounds 1 and 2 showed week inhibitory effects against NO production in LPS-stimulated RAW264.7 cells. All the isolates were investigated for their antifungal activities against drug-resistant Candida albicans.

A comprehensive apoptotic assessment of niloticin in cervical cancer cells: a tirucallane-type triterpenoid from Aphanamixis polystachya (Wall.) Parker.

Pharmacologically active small organic molecules derived from natural resources are prominent drug candidates due to their inherent structural diversity. Herein, we explored one such bioactive molecule, niloticin, which is a tirucallane-type triterpenoid isolated from the stem barks of Aphanamixis polystachya (Wall.) Parker. After initial screening with other isolated compounds from the same plant, niloticin demonstrated selective cytotoxicity against cervical cancer cells (HeLa) with an IC50 value of 11.64 μM. Whereas the compound exhibited minimal cytotoxicity in normal epithelial cell line MCF-10A, with an IC50 value of 83.31 μM. Subsequently, in silico molecular docking studies of niloticin based on key apoptotic proteins such as p53, Fas, FasL, and TNF β revealed striking binding affinity, reflecting docking scores of -7.2, -7.1, -6.8, and -7.2. Thus, the binding stability was evaluated through molecular dynamic simulation. In a downstream process, the apoptotic capability of niloticin was effectively validated through in vitro fluorimetric assays, encompassing nuclear fragmentation. Additionally, an insightful approach involving surface-enhanced Raman spectroscopy (SERS) re-establishes the occurrence of DNA cleavage during cellular apoptosis. Furthermore, niloticin was observed to induce apoptosis through both intrinsic and extrinsic pathways. This was evidenced by the upregulation of upstream regulatory molecules such as CD40 and TNF, which facilitate the activation of caspase 8. Concurrently, niloticin-induced p53 activation augmented the expression of proapoptotic proteins Bax and Bcl-2 and downregulation of IAPs, leading to the release of cytochrome C and subsequent activation of caspase 9. Therefore, the reflection of mitochondrial-mediated apoptosis is in good agreement with molecular docking studies. Furthermore, the anti-metastatic potential was evidenced by wound area closure and Ki67 expression patterns. This pivotal in vitro assessment confirms the possibility of niloticin being a potent anti-cancer drug candidate, and to the best of our knowledge, this is the first comprehensive anticancer assessment of niloticin in HeLa cells.

The Triterpenoids from Munronia pinnata and Their Anti-Proliferative Effects.

Six new tirucallane-type triterpenoids, named munropenes A-F (1-6), were extracted from the whole plants of Munronia pinnata using a water extraction method. Their chemical structures were determined based on detailed spectroscopic data. The relative configurations of the acyclic structures at C-17 of munropenes A-F (1-6) were established using carbon-proton spin-coupling constants (2,3JC,H) and inter-proton spin-coupling constants (3JH,H). Furthermore, the absolute configurations of munropenes A-F (1-6) were determined through high-performance liquid chromatography (HPLC), single-crystal X-ray diffraction, and electronic circular dichroism (ECD) analyses. The antiproliferative effects of munropenes A-F were evaluated in five tumor cell lines: HCT116, A549, HepG2, MCF7, and MDAMB. Munropenes A, B, D, and F (1, 2, 4, and 6) inhibited proliferation in the HCT116 cell line with IC50 values of 40.90, 19.13, 17.66, and 32.62 µM, respectively.

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.

Two new tirucallane-type triterpenes from the aerial parts of Euphorbia retusa

Chemical characterization of the dichloromethane extract of Euphorbia retusa aerial parts by chromatographic methods afforded an inseparable mixture of two new tirucallane-type triterpenoids namely (3β, 24S)- and (3β, 24R)-tirucalla-7,25-diene-3,24-diol (1a and 1b) respectively, together with nine known compounds including six triterpenoids and three phenylpropanoids. Their structures were established on the basis of spectroscopic analyses, including 1D- and 2D- homo- and heteronuclear NMR experiments and mass spectrometry, as well as comparison with data from related compounds. The chemotaxonomic aspects were also discussed.

Chemical constituents from the root bark of Morus alba and their chemotaxonomic significance

Research of detailed chemical constituents from the root bark of Morus alba resulted in the isolation of thirteen compounds, including a new triterpenoid (1), three lupane-type triterpenoids (2-4), two tirucallane-type triterpenoids (5, 6), three ursane-type triterpenoids (7–9), one incompletely cyclized triterpene alcohol (10), and three steroids (11–13). In this study, compound 1 was identified as a new triterpenoid. Among these known compounds, compounds 10 and 12 were firstly obtained from the Moraceae family, compound 5 was mentioned from the Morus genus for the first time, and this was the first report of compounds 6 and 13 in Morus alba species. Furthermore, chemotaxonomic significance of these isolates was also discussed in this paper.

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.

Triterpenoids from Chios mastic gum of Pistacia lentiscus and their inhibition of LPS-induced NO production in RAW 264.7 cells

A phytochemical investigation of mastic, the resinous secretion obtained from the wounds of the trunk and branches of Pistacia lentiscus, led to the isolation of six undescribed triterpenoids (1–6), including two unusual nor-dammarane-type triterpenoids (1 and 2), four tirucallane-type triterpenoids (3–6), together with seven known compounds (7–13). The structures of those undescribed compounds were elucidated by integrating spectroscopic analyses, including NMR, UV, IR, as well as HR-MS data. The absolute configurations of compounds 1 and 2 were confirmed by electronic circular dichroism. Anti-inflammatory evaluation revealed that compounds 5, 8, 9, and 12 exhibited moderate inhibition of the nitric oxide production in RAW264.7 cells with IC50 values ranging from 20.24 to 36.63 μM, compared to that of positive control, dexamethasone (IC50 = 19.85 μM).

Diverse Triterpenoids from Mastic Produced by Pistacia lentiscus and Their Anti-Inflammatory Activities.

Eight undescribed triterpenoids (1-8), including one apotirucallane-type triterpenoid (1), six tirucallane-type triterpenoids (2-7), and one oleanane-type triterpenoid (8), along with ten known compounds (9-18) were isolated from the resins of Pistacia lentiscus. Their structures were elucidated by integrating NMR spectroscopic analyses and ESI-HR-MS. Compounds 5, 11-17 exhibited moderate inhibitory abilities against NO production in LPS-induced RAW264.7 cells, with IC50 values in the range of 18.26-50.37 μM, compared to that of the positive control dexamethasone (IC50 =20.24 μM).

New tirucallane-type triterpenoids from the resin of Boswellia carteriiand their NO inhibitory activities.

Six new tirucallane-type triterpenoids (1-6), along with ten known triterpenoids, were isolated from methylene chloride extract of the resin of Boswellia carterii Birdw. By the application of the comprehensive spectroscopic data, the structures of the compounds were clarified. The experimental electronic circular dichroism spectra were compared with those calculated, which allowed to assign the absolute configurations. Compounds 5 and 6 possesed a 2, 3-seco tirucallane-type triterpenoid skeleton, which were first reported. Their inhibitory activity against NO formation in LPS-activated BV-2 cells were evaluated. Compound 9 showed appreciable inhibitory effect, with an IC50 value of 7.58 ± 0.87 μmol·L-1.

Cytotoxic triterpenoids from Chisocheton pentandrus

Eleven undescribed triterpenoids (pentandrucines A to K) were isolated from the n-hexane extract of the stem bark of Chisocheton pentandrus (Blanco) Merr. These comprised ten undescribed dammarane-type triterpenoids and one undescribed apotirucallane-type triterpenoid. Additionally, two dammarane-type triterpenoids, four apotirucallane-type triterpenoids and two tirucallane-type triterpenoids were also isolated. The chemical structures of pentandrucine A-K, were fully elucidated using 1D and 2D-NMR, and high resolution MS. All of the compounds were evaluated for cytotoxic activity against MCF-7 breast cancer cells in vitro. Melianodiol proved to be the most active with an IC50 of 16.84 μM comparing favourably with Cisplatin (13.2 μM).

Three new tirucallane triterpenoids from the fruits of Chukrasia tabularis and their biological activities

Abstract Three new triterpenoids (1–3), including two new 19 (10 → 9β) abeo-tirucallane derivatives (1–2) and a new tirucallane-type triterpenoid (3), together with two known tirucallane-type triterpenoids (4–5) were isolated from the ethanol extract of the fruits of Chukrasia tabularis. Their structures were elucidated on the basis of 1D and 2D NMR spectroscopic analyses and MS data. The isolated triterpenoids 1 and 2 exhibited anti-inflammatory activities with IC50 values of 75.98 ± 2.12 and 24.86 ± 1.16 μM, respectively. Compound 5 showed cytotoxic activities against the selected tumor cell lines.

Structure elucidation and absolute configuration determination of C26, C27 and C30 tirucallane triterpenoids from the leaves of Picrasma quassioides (D. Don) Benn

Seven undescribed tirucallane-type triterpenoids, kumunorquassins A‒E and kumuquassins K and L, along with nine known analogues, have been isolated from the leaves of Picrasma quassioides (D. Don) Benn. Their structures and absolute configurations were elucidated based on comprehensive spectroscopic analyses, single-crystal X-ray diffraction analysis and electronic circular dichroism (ECD). The absolute configuration of cornusalterin J was unequivocally determined by X-ray diffraction based on its p-bromobenzoate derivative. A brief approach was presented in our study, which could rapidly and conveniently determine the relative and absolute configurations of OCH3-23 of kumuquassin L and cornusalterins J, H and G depending on the chemical shift differences (Δδ) of C-24 and C-25 and the chemical shifts of C-23, H-23 and H-24. In addition, the cytotoxicities of these compounds against two human tumour cell lines (HepG2 and Hep3B) were evaluated.

Triterpenoids from Picrasma quassioides with their cytotoxic activities

Abstract Eleven triterpenoids, including a new tirucallane-type triterpenoid and a new natural product, were isolated from Picrasma quassioides. Their structures were elucidated by extensive spectroscopic analysis. All isolates were evaluated for their cytotoxic activities against Hep3B and HepG2 cell lines. Compounds 1 and 4 showed moderate cytotoxic activities toward the HepG2 cell at 50 μM, and 1 and 4 displayed equivalent effect to the positive control on Hep3B cell.

Advances in studies on structure and pharmacological activities of natural tirucallane-type triterpenoids

The tirucallane-type triterpenoids, composed of six isoprene units, belong to a group of tetracyclic triterpenoids. Although the naturally-derived tirucallane-type triterpenoids were found in a small amount, the kind of compounds showed various structures, which consist of apo-type, linear said-chain-type and cyclolike said-chain-type and broad bioactivities, such as cytotoxicity, anti-inflammation, antioxidation and anti-plasmin, etc. This paper summarized origins, structures and bioactivities of tirucallane-type triterpenoids in recent ten years. The future research and exploration of tirucallane-type triterpenoids were discussed and prospected.

Chemical constituents from the barks of Melia azedarach and their PTP1B inhibitory activity

One new long-chain ester derivative of trans-ferulic acid 1 and one natural tirucallane-type triterpenoid 2, together with forty known compounds (3-42), were isolated from the barks of Melia azedarach. Their structures were established on the basis of spectroscopic data interpretation. Compounds 7, 9, 10, 12, 13 showed significant inhibitory activities against PTP1B with IC50 values of 13.82 ± 1.29 μM, 13.29 ± 2.26 μM, 20.27 ± 0.52 μM, 24.36 ± 1.25 μM, 15.23 ± 0.6 μM, respectively.

Four new tirucallane-type triterpenoids from Sapindus mukorossi Gaertn. flowers induced neurite outgrowth in PC12 cells related to insulin-like growth factor 1 receptor/phosphoinositide 3-kinase/extracellular regulated protein kinase signaling pathway

Four new tirucallane-type saponins (i.e., sapinmusaponin S–V, which include one new structure and three new stereoisomers) and a known compound sapinmusaponin G were isolated from the flowers of Sapindus mukorossi. All of them could significantly induce neurite outgrowth of PC12 cells. The structures of active compounds were determined using spectroscopic data and chemical derivatization. Specific inhibitor experiments and Western blot analysis of sapinmusaponin S, which is the most active compound, were performed. Results indicated that the insulin-like growth factor 1 receptor/phosphoinositide 3-kinase/extracellular regulated protein kinase signaling pathway is involved in this action.

Toonamicrocarpavarin, a new tirucallane-type triterpenoid from Toona Ciliata

Toonamicrocarpavarin (1), a new tirucallane-type triterpenoid, along with eight known ones, piscidinol A (2), toonaciliatavarin E (3), toonayunnanin A (4), 7-acetyneotrichilenone (5), hispidol A (6), odoratone (7), phellochin (8), toonaciliatavarin D (9), were isolated from T. ciliata. Their structures were identified on the basis of ESIMS, HREIMS and 1 D/2D NMR analysis. The cytotoxic activity of the new compound was also evaluated. All compounds were obtained from T. ciliata for the first time, which plays an important role in chemotaxonomy of the plant T. ciliata.

New tirucallane triterpenoids from Picrasma quassioides with their potential antiproliferative activities on hepatoma cells

Seven new tirucallane-type triterpenoids (1–7), kumuquassin A-G, along with 20 known analogues (8–27) were isolated from the stems of Picrasma quassioides. The structures and the absolute configurations of new compounds were elucidated by spectroscopic data, electronic circular dichroism (ECD) spectroscopic analyses and quantum ECD calculations. Notably, kumuquassin A (1) contains a rare Δ17, 20 double bond, kumuquassin B (2) is the first example of tirucallane triterpenoid possessing a 5/3 biheterocyclic ring system at the side chain. All the compounds were screened for the cytotoxicity against two human hepatoma cell lines, HepG2 and Hep3B, and several compounds exhibited promising activity. The most potential compound 3 was selected for cell cycle analysis, which showed that 3 could cause an accumulation of HepG2 cells at subG1 peak. Annexin V-FITC/PI staining further confirmed that compound 3 caused death of hepatoma cells through apoptosis induction.