Antitubercular Activity Increase in Labdane Diterpenes from Copaifera Oleoresin through Structural Modification

Silva, Aline N.; Soares, Ana Carolina Ferreira; Cabral, Mirela M. W.; Andrade, Alex Rafael Pedroso de; Silva, Marilza B. M. da; Martins, Carlos Henrique Gomes; Veneziani, Rodrigo Cássio Sola; Ambrósio, Sérgio Ricardo; Bastos, Jairo K.; Heleno, Vladimir Constantino Gomes

doi:10.21577/0103-5053.20160268

Cited by 8 publications

(9 citation statements)

References 17 publications

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“…They were isolated from a Copaifera langsdorffii oleoresin by several chromatographic techniques, such as vacuum liquid chromatography, flash chromatography, and thin layer chromatography, as described previously . These compounds were identified on the basis of their 1 H and 13 C NMR data and comparison with literature data …”

Section: Methodsmentioning

confidence: 99%

“…4 These compounds were identified on the basis of their 1 H and 13 C NMR data and comparison with literature data. 12 were dissolved in a MeOH/H 2 O (9:1 v/v + 0.1% ammonium acetate) solution and directly infused into the ionization source with the aid of a syringe pump (Harvard, Holliston, MA, USA). The source and operating parameters were optimized as follows: capillary voltage = 2.5 kV, cone voltage = −40 V, source temperature = 150°C, desolvation temperature (N 2 ) = 350°C, and desolvation gas flow = 600 L/h.…”

Section: Isolation and Identification Of Compounds 1 Tomentioning

confidence: 99%

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Electrospray ionization tandem mass spectrometry of labdane‐type acid diterpenes

et al. 2018

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Copaifera (Leguminoseae) species produce a commercially interesting oleoresin that displays several biological activities, including antimicrobial and anti-inflammatory properties. Labdane-type diterpenes are the main chemical constituents of these oleoresins, and copalic acid is the only compound that has been detected in all Copaifera oleoresins. In this study, we investigate some aspects of the gas-phase fragmentation reactions involved in the formation of the product ions from the deprotonated compounds (-)-ent-copalic acid (1), (-)-ent-3β-hydroxy-copalic acid (2), (-)-ent-3β-acetoxy-copalic acid (3), and (-)-ent-agathic acid (4) by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and multiple stage mass spectrometry (MS ). Our results reveal that the product ion with m/z 99 is common to all the analyzed compounds, whereas the product ion with m/z 217 is diagnostic for compounds 2 and 3. Moreover, only compound 4 undergoes CO (44 u) and acetic acid (60 u) elimination from the precursor ion. Thermochemical data obtained by computational chemistry at the B3LYP/6-31G(d) level of theory support the proposed ion structures. These data helped us to identify these compounds in a crude commercial Copaifera langsdorffii oleoresin by selective multiple reaction monitoring (MRM). Finally, a precursor ion scan (PIS) strategy aided screening of labdane-type acid diterpenes other than 1 to 4 in the same Copaifera oleoresin sample and led us to propose the structures of 8,17-dihydro-ent-agathic acid (5) and 3-keto-ent-copalic acid (6), which have not been previously reported in Copaifera oleoresins.

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Section: Methodsmentioning

confidence: 99%

Section: Isolation and Identification Of Compounds 1 Tomentioning

confidence: 99%

Electrospray ionization tandem mass spectrometry of labdane‐type acid diterpenes

et al. 2018

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“…Based on the comprehensive application of copaiba oil in folk medicine and its recent popularity in the cosmetics and pharmaceutical industries, COPA and its derivatives have been subjected to various scientific studies aiming to prove their biological activities. Previous studies revealed that COPA possesses interesting bioactivities, including antibacterial 20 , 21 , antifungal 22 , anti-inflammatory 23 , 24 , anti-tuberculosis 25 and cancer cytotoxic 26 properties. Studies of COPA derivatives that offered superior bioactivities than that of the parent COPA have also been reported.…”

Section: Introductionmentioning

confidence: 99%

The amide derivative of anticopalic acid induces non-apoptotic cell death in triple-negative breast cancer cells by inhibiting FAK activation

Chawengrum,

Luepongpatthana,

Thongnest

et al. 2023

Sci Rep

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Anticopalic acid (ACP), a labdane type diterpenoid obtained from Kaempferia elegans rhizomes, together with 21 semi-synthetic derivatives, were evaluated for their cancer cytotoxic activity. Most derivatives displayed higher cytotoxic activity than the parent compound ACP in a panel of nine cancer cell lines. Among the tested compounds, the amide 4p showed the highest cytotoxic activity toward leukemia cell lines, HL-60 and MOLT-3, with IC50 values of 6.81 ± 1.99 and 3.72 ± 0.26 µM, respectively. More interestingly, the amide derivative 4l exhibited cytotoxic activity with an IC50 of 13.73 ± 0.04 µM against the MDA-MB-231 triple-negative breast cancer cell line, which is the most aggressive type of breast cancer. Mechanistic studies revealed that 4l induced cell death in MDA-MB-231 cells through non-apoptotic regulated cell death. In addition, western blot analysis showed that compound 4l decreased the phosphorylation of FAK protein in a concentration-dependent manner. Molecular docking simulations elucidated that compound 4l could potentially inhibit FAK activation by binding to a pocket of FAK kinase domain. The data suggested that compound 4l could be a potential FAK inhibitor for treating triple-negative breast cancer and worth being further investigated.

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“…Labdane diterpenes are highlighted due to their broad biological activities, [5] such as antiinflammatory, [6] immunosuppressive, [7] cytotoxic, [8] and antimicrobial [9] and display an enormous potential for pharmaceutical applications. [10 -12] The labdane diterpene ent-labd-8( 17)-en-15,18dioic acid is a secondary metabolite commonly found in the oleoresins extracted from Copaifera tree trunks [13] whose production exceeded 2,200 tons from 2010 to 2020.…”

Section: Introductionmentioning

confidence: 99%

Production of More Potent Anti‐Candida Labdane Diterpenes by Biotransformation Using Cunninghamella elegans

Sousa

Teixeira

Freitas

et al. 2022

Chemistry & Biodiversity

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Candida species are responsible for causing invasive candidiasis with high mortality rate and their resistance to available antifungal drugs is a major clinical challenge. Biotransformation process of the labdane diterpene ent-labd-8( 17)-en-15,18-dioic acid (1) carried out with Cunninghamella elegans afforded five new derivatives (compounds 2-6). Unusual regioselective hydroxylation of the methyl group at the C-20 position of labdanetype diterpene was achieved and all compounds were subjected to cytotoxicity and antifungal evaluations. Compound 1 and its derivatives were not cytotoxic to normal (MCF-10A) and tumor (MCF-7) cell lines. Compounds 2 and 3 exhibited fungistatic activity against all tested Candida strains at lower concentrations than fluconazole. Both compounds also showed the strongest fungicidal activity against C. albicans, which is the most prevalent fungal agent involved in candidemia.

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Antitubercular Activity Increase in Labdane Diterpenes from Copaifera Oleoresin through Structural Modification

Cited by 8 publications

References 17 publications

Electrospray ionization tandem mass spectrometry of labdane‐type acid diterpenes

Electrospray ionization tandem mass spectrometry of labdane‐type acid diterpenes

The amide derivative of anticopalic acid induces non-apoptotic cell death in triple-negative breast cancer cells by inhibiting FAK activation

Production of More Potent Anti‐Candida Labdane Diterpenes by Biotransformation Using Cunninghamella elegans

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