Tirucallane-type Triterpenoids Research Articles

Limonoids and triterpenoid from fruit of Swietenia macrophylla

Five new limonoids, swieteliacates A–E (1–5) and a tirucallane-type triterpenoid, swietesenin (6), together with four known compounds (7–10) were isolated from fruit of Swietenia macrophylla. Their structures were determined by spectroscopic analyses. The new compounds were tested in vitro for their cytotoxic effects against five human cancer cell lines. Compound 2 exhibited moderate cytotoxic activities against SW480 and HL-60 cancer cell lines with IC50 values of 30.6 and 32.9μM, respectively.

Chemical constituents from the fruiting bodies of Phellinus igniarius

A new tirucallane-type triterpenoid igniarine (1), and four known compounds meshimakobnol A (2), meshimakobnol B (3), ergosterol (4) and ergosterol peroxide (5), were purified from the methanol extracts of the fruiting bodies of Phellinus igniarius (DC. ex Fr.) Quél. The structure of 1 was elucidated using a combination of 1D and 2D NMR techniques and HR-ESI-MS analyses. In addition, the isolated compounds were examined for their cytotoxicity against several tumour cell lines and part of the tested compounds demonstrated weak cytotoxicity.

Cytotoxic Tirucallane and Apotirucallane Triterpenoids from the Stems of Picrasma quassioides.

Phytochemical investigation on the stems of Picrasma quassioides led to the isolation of a novel compound, picraquassin A (1), with an unprecedented 21,24-cycloapotirucallane skeleton, and four new apotirucallane-type triterpenoids (2-5), together with 15 new tirucallane-type triterpenoids (6-20) and 10 known tirucallane-type triterpenoids (21-30). To our knowledge, this is the first report demonstrating the presence of apotirucallane-type triterpenoids in the genus Picrasma. The structures of the new compounds were determined based on spectroscopic data interpretation. Cytotoxicities of the isolated compounds were evaluated using three human cancer cell lines, MKN-28, A-549, and MCF-7. Compound 2 exhibited the most potent activity against MKN-28 cells with an IC50 value of 2.5 μM. Flow cytometry and Western blot analysis revealed that 2 induces the apoptosis of MKN-28 cells via activating caspase-3/-9, while increasing Bax and Bad and decreasing Bcl-2 expression levels.

Tirucallane-type triterpenoids from the fruits of Phellodendron chinense Schneid and their cytotoxic activities

Eleven triterpenoids were isolated from the fruits of Phellodendron chinense Schneid, and their structures were determined by spectroscopic analysis. The results show that four new tirucallane-type triterpenoids 1, 2, 5, and 6 and seven known compounds 3, 4, 7, 8, 9, 10, and 11 were isolated. Structurally, compound 6 was uncommon; it has a chlorine atom instead of a methyl group at the C-20 position. The cytotoxicities of the compounds was evaluated against the in vitro proliferation of four human tumor cell lines HEL, K562, MDA, and PC3 using adriamycin as the positive control. Compound 1 showed a similar cytotoxicity as the positive control; compounds 3 and 10 showed moderate cytotoxicities compared to the control (P<0.05). This indicates that these compounds have great potential for the development of new antitumor drugs.

Minor secondary metabolites from the bark of Entandrophragma congoënse (Meliaceae)

Two new tirucallane-type triterpenoids were isolated from the bark of Entandrophragma congoënse (Meliaceae) along with five known compounds gladoral A, bipendensin, 4-hydroxymethyl-3,5-dimethyldihydrofuran-2(3H)-one, scopoletin and 5,7-dimethoxy-6-hydroxycoumarin. Their structures were elucidated by means of spectroscopic analyses including 1D and 2D-NMR spectroscopy, high resolution mass spectrometric data as well as the comparison of data with those reported in the literature. The tested compounds (1–4) displayed moderated antiplasmodial activity against erythrocytic stages of chloroquine-resistant Plasmodium falciparum strain NF54 and low cytotoxicity on L6 cell lines. All the isolated compounds are reported for the first time from the genus Entandrophragma.

Tirucallane-type triterpenoids from the fruit of Ficus carica and their cytotoxic activity.

Nine new tirucallane-type triterpenoids, ficutirucins A-I (1-9), were isolated from the fruit of Ficus carica. Their structures were established on the basis of spectroscopic data and chemical methods. All isolates were evaluated for their cytotoxic activities against three human cancer cell lines, MCF-7, HepG-2, and U2OS. Compounds 1-3, 6, 7, and 9 exhibited moderate cytotoxic activities with IC50 values of 11.67-45.61 µM against one or more of the three cancer cell lines.

Tirucallane‐Type Triterpenoids from Celastrus stylosusWall.

AbstractTwo new tirucallane‐type triterpenoids, (24Z)‐tirucalla‐7,24‐diene‐3β,11β,26‐triol (1) and (3S,24R)‐tirucall‐7‐ene‐3,24,25‐triol (2), along with the known compound celastrol (3), were isolated from the root barks of Celastrus stylosus Wall. The structures of 1–3 were established by spectroscopic methods, including extensive 2D NMR and MS analyses. It is the first report on tirucallane‐type triterpenoids from the genus Celastrus and may be of vital chemotaxonomic significance.

Triterpenoids from the fruits of Azadirachta indica (Meliaceae)

Four new triterpenoids, indicalilacols A-D (1–4), were isolated from the MeOH extract of the fruits of Azadirachta indica, including a new 19(10→9β)abeo-tirucallane derivative, two new tirucallane-type triterpenoids, and a new euphane-type triterpenoid, along with three known tirucallane-type triterpenoids. Their structures were elucidated on the basis of spectroscopic analyses. The absolute configuration of 2 was elucidated by the chemical conversion of 2 into 21-oxo-melianodiol 24,25-acetonide. Compounds 2, 6–8 exhibited moderate cytotoxicity against three human cancer cell lines, including multidrug-resistant (MDR) cancer cells (KB-C2). Although compound 5 was not cytotoxic against any of the tested cancer cell lines, 5 showed cytotoxicity against KB-C2 cells in the presence of 2.5μM colchicine, suggesting that 5 might have an MDR-reversal effect.

Limonoids from the fruits of Melia azedarach and their cytotoxic activities

Thirty-one limonoids and one tirucallane-type triterpenoid were isolated from the fruits of Melia azedarach (Meliaceae). The structures of 14 of these isolated compounds were elucidated on the basis of spectroscopic analyses and comparison with literature. All of these compounds were evaluated for their cytotoxic activities against HL60, A549, AZ521, and SK-BR-3 human cancer cell lines. Meliarachin C (IC50 0.65 μM) and 3-O-deacetyl-4'-demethyl-28-oxosalannin (IC50 2.8 μM) exhibited potent cytotoxic activity against HL60 cells, and this was demonstrated mainly due to the induction of apoptosis by flow cytometry. Western blot analysis suggested that both compounds induced apoptosis via both the mitochondrial and death receptor-mediated pathways. In addition, 25 compounds were evaluated for their inhibitory effects against the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells.

Tetracyclic triterpenoids and terpenylated coumarins from the bark of Ailanthus altissima (“Tree of Heaven”)

Tetracyclic triterpenoids (named as altissimanins A-E, 1-5) and a terpenylated coumarin (denominated as altissimacoumarin G, 6), along with fifteen known compounds (7-21) were isolated from the bark of Ailanthus altissima. Structures of compounds 1-6 were established by spectroscopic methods and chemical transformations. Altissimanin A (1) is a tirucallane-type triterpenoid bearing an uncommon oxetane ring in the side-chain, while altissimanins D (4) and E (5) are two unprecedented dimers each consisting of one tirucallane-type and one dammarane-type triterpenoid moiety. All the isolates were evaluated for their cytotoxic effects against a small panel of human cancer cell lines.

Cytotoxic and Anti-inflammatory Triterpenoids from Toona ciliata

Toonaciliatavarins A-H (1-8), including three new protolimonoids (1-3), two new tirucallane-type triterpenoids (4 and 5), and three new tetranortriterpenoids (6-8), and 10 known compounds were isolated from the stem barks of Toona ciliata Roem. var. henryi. Their structures were identified on the basis of spectroscopic analysis. The absolute configurations of 2 and 8 were determined by ECD calculation. The new isolates were evaluated for their cytotoxicities using six human cancer cell lines and also for their inhibitory effects on lipopolysaccharide-induced nitric oxide production in RAW264.7 cells. Compounds 4 and 5 showed moderate cytotoxicities, and the protolimonoids (1-3) exhibited marked inhibitory effects on LPS-stimulated NO production.

Limonoids from Melia azedarach with Deterrent Activity against Insects

The ethanolic extract of ripe fruits of Melia azedarach (Meliaceae) and its subfractions were tested against four insect species, portraying important agricultural pests. Five limonoids were isolated: two tirucallane type triterpenoids never isolated before from this species (21α-methylmelianodiol, 21β-ethylmelianodiol), as well as three ring C-seco limonoids previously reported on this tree (1-O-detigloyl-1-O-cinnamoylohchinolal, 1-O-detigloyl-1-O-benzoylohchinolal and ohchinolal). The complete NMR data of these natural products are reported here. Different patterns of activity were found among the products tested against the different pest models, emphasizing the value of testing potential biocontrol products against different insect targets.

Tirucallane-Type Triterpenoids from Dysoxylum lenticellatum

Ten new tirucallane-type triterpenoids, represented by a rearranged skeleton dysolenticin A (1), dysolenticin B (2), a rare trinortriterpenoid dysolenticin C (3), three tirucallane triterpenoid derivatives with a hemiketal moiety dysolenticins D-F (4-6), dysolenticins G-I (7, 9, 10), and the new alkaloid dysolenticin J (12), together with seven known analogues were isolated from the twigs and leaves of Dysoxylum lenticellatum. Their structures were elucidated by extensive spectroscopic methods, and those of compounds 1, 3, 4, 6, and 10 were confirmed by single-crystal X-ray diffraction experiments. Dysolenticin J (12) showed significant vasodilative effects on intact rat aortic rings with a diastolic degree of 87.4% at 10 μg/mL.

Limonoids from the fruits of Melia toosendan

Four ( 1– 4) new and seven known limonoids were isolated from the EtOH extract of the fruits of Melia toosendan. The structures of the new compounds were established on the basis of spectroscopic methods to be 12- O-methyl-1- O-deacetylnimbolinin B ( 1), 12- O-methy-1- O-tigloyl-1- O-deacetylnimbolinin B ( 2), 12- O-ethylnimbolinin B ( 3), and 1- O-cinnamoyl-1- O-debenzoylohchinal ( 4). Additionally, two new tirucallane-type triterpenoids, named meliasenins S ( 5) and T ( 6), were obtained from the same fractions during purification of the limonoids.

Cytotoxic Triterpenoid Constituents from Two Plants of the Family Meliaceae

For their interesting structures and significant biological activities, triterpenoids from plants of the family Meliaceae have been the research focus for several years. In our initial screening of the Meliaceae species, the extracts of Aglaia abbreviata C. Y. Wu and Aphanamixis grandifolia Bl exhibited some inhibitory activity against a panel of tumor cell lines. Phytochemical investigations on the two plants afforded six new dammarane-type triterpenoids, named aglaiabbreviatins A-F (1–6), along with twenty known triterpenoids from the stems of A. abbreviata, and twenty new tirucallane-type triterpenoids, named aphagranins A-T (7–26), along with ten known triterpenoids from the stem bark of A. grandifolia. Their structures were elucidated mainly by spectroscopic evidence. Of them, compound 9 has a maleimide ring in the side-chain; compound 19 incorporates a unique pyrrole ring, representing the first protolimonoid with such a moiety. All the new isolates were evaluated for their cytotoxicity against several tumor cell lines including multidrug resistant ones. Compounds 3–6, 11, 14–16 were found to have cytotoxicity to the tumor cell lines used, especially, compounds 6, 14, and16 showed the most potent activity.

Triterpenoids and Sterones from the Stem Bark of Ailanthus altissima

One new tirucallane-type triterpenoid, alianthusaltinin A (1), one new C(29)sterone, alianthaltone A (2), and 12 known compounds have been isolated from the stem bark of Ailanthus altissima. The structures of new compounds were identified by means of spectroscopic methods. Compound 3 was isolated from natural sources for the first time, and compounds 4, 5, and 9 were isolated from this plant for the first time.

Triterpenoids from the leaves of Toona ciliata

One new limonoid, toonaciliatone A (1), and one new tirucallane-type triterpenoid, toonaciliatine A (4), along with three known compounds, methyl-3β-acetoxy-1-oxomelic-14(15)-enate (2), perforin A (3), and cholest-14-ene-3,7,24,25-tetrol-21,23-epoxy-21-methoxy-4,4,8-trimethyl-3-(3-methyl-2-butenoate) (5), were isolated from the leaves of Toona ciliata. The structures of the new compounds were established by spectroscopic methods.

Limonoids and Triterpenoids from the Stem Bark of Melia toosendan

Four new limonoids (1, 3, 4, 6), named meliatoosenins A-D, eight new euphane- and tirucallane-type triterpenoids (8-15), named meliasenins A-H, and 13 known compounds have been isolated from the stem bark of Melia toosendan. The structures of new compounds were established on the basis of 1D and 2D NMR experiments ((1)H-(1)H COSY, HSQC, HMBC, and ROESY).

Canthin-6-one Alkaloids and a Tirucallanoid from Eurycoma longifolia and Their Cytotoxic Activity against a Human HT-1080 Fibrosarcoma Cell Line

Phytochemical investigation of the stems of Eurycoma longifolia Jack led to the isolation of two new canthin-6-one alkaloids, 4,9-dimethoxycanthin-6-one (1) and 10-hydroxy-11-methoxycanthin-6-one (2), and a new tirucallane-type triterpenoid, 23,24,25-trihydroxytirucall-7-en-3,6-dione (3), along with 37 known compounds. Among these, an oxasqualenoid (4) was isolated as a natural product for the first time. The structures of the isolates were elucidated by spectroscopic and mass spectrometric means. All the isolates were evaluated for their cytotoxic activity against a HT-1080 human fibrosarcoma cell line. Among them, 9,10-dimethoxycanthin-6-one (14, IC50 = 5.0 microM), 10-hydroxy-9-methoxycanthin-6-one (15, IC50 = 7.2 microM), dihydroniloticin (18, IC50 = 8.2 microM), and 14-deacetyleurylene (34, IC50 = 3.2 microM) displayed stronger activity than the positive control 5-FU (IC50 = 9.2 microM).

Terpenoids from Toona ciliata

Three new norlimonoids (1-3), two new tirucallane-type triterpenoids (4 and 5), and a new pimaradiene-type diterpenoid (6), along with two known limonoids and eight known tirucallane-type triterpenoids, were isolated from the leaves and twigs of Toona ciliata. Their structures were elucidated on the basis of spectroscopic data. Toonaciliatin M (6) showed moderate antifungal activity against Trichophyton rubrum with an MIC of 12.5 microg/mL.