Determination of the absolute configuration of the diterpene tonantzitlolone B

Busch, Torsten; Schuster, Hannah; Kirschning, Andreas

doi:10.1016/j.tetlet.2008.06.105

Cited by 6 publications

(6 citation statements)

References 7 publications

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“…Compound 6 (tonantzitlolone F) gave a molecular formula of C 26 , together with HMBC cross-peaks from H-3′, H-6′, and H-8 to the carbonyl C-1′ at δ C 165.4, revealed the presence of a nicotinyl ester moiety attached at C-8 on the macrocycle. 29 Due to a preferential ionization of nonbonding electrons of the nitrogen atom of the nicotinate moiety, the in-source fragmentation of 6 did not lead to the cleavage of the side chain, as for the other members of this chemical series.…”

Section: Resultsmentioning

confidence: 99%

“…25 These compounds showed interesting cytotoxic activities against human kidney and breast cancer cell lines. 26 Tonantzitlolone A was also isolated from the aerial parts of Sebastania macrocarpa, another Euphorbiaceae species collected in Brazil. 27 In this paper are reported the LC-MS-guided isolation, structure elucidation, and anti-CHIKV properties of three known (1−3) and six new tonantzitlolones (4−9), tonantzitloic acid (10), and three new (11, 13, and 15) and two known tigliane diterpenes (12 and 14) isolated from the ethyl acetate extract of S. lineata leaves.…”

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confidence: 99%

“…More recently, Dräger and colleagues reported the isolation of two novel diterpenes, tonantzitlolones A and B, sharing the rare flexibilane backbone, from S. sanguinolenta. These compounds showed interesting cytotoxic activities against human kidney and breast cancer cell lines . Tonantzitlolone A was also isolated from the aerial parts of Sebastania macrocarpa , another Euphorbiaceae species collected in Brazil …”

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Antiviral Activity of Flexibilane and Tigliane Diterpenoids from Stillingia lineata

et al. 2015

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In an effort to identify new potent and selective inhibitors of chikungunya virus and HIV-1 and HIV-2 virus replication, the endemic Mascarene species Stillingia lineata was investigated. LC/MS and bioassay-guided purification of the EtOAc leaf extract using a chikungunya virus-cell-based assay led to the isolation of six new (4-9) and three known (1-3) tonantzitlolones possessing the rare C20-flexibilane skeleton, along with tonantzitloic acid (10), a new linear diterpenoid, and three new (11, 13, and 15) and two known (12 and 14) tigliane-type diterpenoids. The planar structures of the new compounds and their relative configurations were determined by spectroscopic analysis, and their absolute configurations were determined through comparison with literature data and from biogenetic considerations. These compounds were investigated for selective antiviral activity against chikungunya virus (CHIKV), Semliki Forest virus, Sindbis virus, and, for compounds 11-15, the HIV-1 and HIV-2 viruses. Compounds 12-15 were found to be the most potent and are selective inhibitors of CHIKV, HIV-1, and HIV-2 replication. In particular, compound 14 inhibited CHIKV replication with an EC50 value of 1.2 μM on CHIKV and a selectivity index of >240, while compound 15 inhibited HIV-1 and HIV-2 with EC50 values of 0.043 and 0.018 μM, respectively. It was demonstrated further that potency and selectivity are sensitive to the substitution pattern on the tigliane skeleton. The cytotoxic activities of compounds 1-10 were evaluated against the HCT-116, MCF-7, and PC3 cancer cell lines.

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confidence: 99%

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Antiviral Activity of Flexibilane and Tigliane Diterpenoids from Stillingia lineata

et al. 2015

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“…Selected relevant NOESY correlations are illustrated in the X-ray structure depicted in Figure 1(a), since the conformation determined by X-ray analysis (vide infra) was in agreement with the H-H dihedral angles deduced from the J H-H 1 H NMR coupling constants. Some fragments of this compound were previously synthesized [30], the total synthesis has also been completed [24,31], and its absolute configuration has been established [32], as depicted in formula 7.…”

Section: Resultsmentioning

confidence: 99%

Tonantzitlolone A and other cytotoxic constituents of Sapium macrocarpum (Euphorbiaceae)

et al. 2017

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Sapium macrocarpum (Euphorbiaceae) is a tropical tree located mainly in the southern part of Mexico and in Central America, and it is used in the Mayan traditional medicine for the treatment of several skin diseases. The dichloromethane-MeOH extract of the aerial parts displayed cytotoxic activity against certain cancer cell lines. Lupeol (1), lupenone (2), sitostenone (3), β-sitosterol (4), stigmasterol (5), sitosteryl β-D-glucopyranoside (6) and the rare diterpene tonantzitlolone A (7) were characterized from this extract. The structural analysis allowed the 1H NMR reassignments for H-12α and H-12β, and for H-13α and H-13β of tonantzitlolone A (7). The cytotoxic activity of compounds 1-3, 6 and 7 was evaluated against selected cancer cell lines. Compounds 3, 6 and 7 displayed clear activity against K562 (leukemia). This is the first report on the chemical constituents of S. macrocarpum, and points out that this species is an additional source of tonantzitlolone A. Compound 7 has only been reported previously from species of the Stillingia, Sebastiania and Sapium genera, which belong to the Hippomaninae subtribe of the family Euphorbiaceae.

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“…The anti-CHIKV effect for TNZ-A has been described (Olivon et al 2015;Techer et al 2015;Wardana et al 2021). Regarding cytotoxicity, biological evaluation indicated high activity and selectivity against human breast and kidney cancer cell lines for both compounds (Busch et al 2008;Busch et al 2016); however, cytotoxicity was also recorded against colorectal and prostate cell lines (Olivon et al 2015) and leukemia cells (Novillo et al 2017). TNZ-A exerts antitumor action by activating PKCθ, a protein kinase C isoform (Sourbier et al 2015), and induces cytostatic effect via inhibition of the mitotic motor protein kinesin-5 (Pfeffer et al 2016).…”

Section: Introductionmentioning

confidence: 99%

Antitumor and antiangiogenic effects of Tonantzitlolone B, an uncommon diterpene from Stillingia loranthacea

Abrantes

Batista

Mangueira

et al. 2021

Naunyn-Schmiedeberg's Arch Pharmacol

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Natural products have played a pivotal role for the discovery of anticancer drugs. Tonantzitlolones are flexibilan-type diterpenes rare in nature; therefore, few reports have shown antiviral and cytotoxic activities. This study aimed to investigate the in vivo antitumor action of Tonantzitlolone B (TNZ-B) and its toxicity. Toxicity was evaluated in mice (acute and micronucleus assays). Antitumor activity of TNZ-B (1.5 or 3 mg/kg intraperitoneally -i.p.) was assessed in Ehrlich ascites carcinoma model. Angiogenesis and reactive oxygen species (ROS) and nitric oxide (NO) production were also investigated, in addition to toxicological effects after 7-day treatment. The LD 50 (lethal dose 50%) was estimated at around 25 mg/kg (i.p.), and no genotoxicity was recorded. TNZ-B reduced the Ehrlich tumor's volume and total viable cancer cell count (p < 0.001 for both). Additionally, TNZ-B reduced peritumoral microvessel density (p < 0.01), suggesting antiangiogenic action. Moreover, a decrease was observed on ROS (p < 0.05) and nitric oxide (p < 0.001) levels. No significant clinical findings were observed in the analysis of biochemical, hematological, and histological (liver and kidney) parameters. In conclusion, TNZ-B exerts antitumor and antiangiogenic effects by reducing ROS and NO levels and has weak in vivo dose-repeated toxicity. These data contribute to elucidate the antitumor action of TNZ-B and point the way for further studies with this natural compound as an anticancer drug.

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Determination of the absolute configuration of the diterpene tonantzitlolone B

Cited by 6 publications

References 7 publications

Antiviral Activity of Flexibilane and Tigliane Diterpenoids from Stillingia lineata

Antiviral Activity of Flexibilane and Tigliane Diterpenoids from Stillingia lineata

Tonantzitlolone A and other cytotoxic constituents of Sapium macrocarpum (Euphorbiaceae)

Antitumor and antiangiogenic effects of Tonantzitlolone B, an uncommon diterpene from Stillingia loranthacea

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