In vitro antileishmanial and antitrypanosomal activity of compounds isolated from the roots of Zanthoxylum tingoassuiba

Five coumarins (5,7,8-trimethoxycoumarin (1), sabandin (2), cubreuva lactone (3), 5,7-dimethoxycoumarin (5) and braylin (6)), seven furoquinoline alkaloids (isopimpinelin (4), pteleine (7), maculine (8), skimianine (10), robustine (11), y-fagarine (12) and dictamine (13) and the furofuran type lignin syringaresinol (9)) have been identified for the first time in the roots of Zanthoxylum tingoassuiba A. St.-Hil., Rutaceae. Pure compounds 1, 6, 9, 12 were tested against Leishmania amazonensis parasites and epimastigotes forms of Trypanosoma cruzi. All the tested products displayed an antiparasitic activity similar to that of the positive controls (benznidazole and amphotericin B). Compound 9 was the most active against both parasites with IC₅₀ values of 11.98 µM and 7.55 µM against L. amazonensis and T. cruzi, respectively.

Keywords
Leismaniasis; Trypansomiasis; Coumarins; Furoquinoline alkaloids; Syringaresinol

Authorship

Rafael S. Costa ^** Corresponding author. E-mail:rafael.costa@ufba.br (R.S. Costa).

Departamento do Medicamento, Faculdade de Farmácia, Universidade Federal da Bahia, Salvador, BA, BrazilUniversidade Federal da BahiaBrazilSalvador, BA, BrazilDepartamento do Medicamento, Faculdade de Farmácia, Universidade Federal da Bahia, Salvador, BA, Brazil

Instituto de Química, Universidade Federal da Bahia, Salvador, BA, BrazilUniversidade Federal da BahiaBrazilSalvador, BA, BrazilInstituto de Química, Universidade Federal da Bahia, Salvador, BA, Brazil

Otávio P. Souza Filho

Otávio C.S. Dias Júnior

Laboratório de Biologia Parasitária, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BA, BrazilFundação Oswaldo CruzBrazilSalvador, BA, BrazilLaboratório de Biologia Parasitária, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BA, Brazil

Jaqueline J. Silva

Mireille Le Hyaric

Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Juiz de Fora, Juiz de Fora, MG, BrazilUniversidade Federal de Juiz de ForaBrazilJuiz de Fora, MG, BrazilDepartamento de Química, Instituto de Ciências Exatas, Universidade Federal de Juiz de Fora, Juiz de Fora, MG, Brazil

Marcos A.V. Santos

1 Present address: Laboratório de Toxoplasmose e outras Protozooses, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz; Fiocruz/RJ, Brazil.

Eudes S. Velozo

Authors’ contributions

RSC contributed in collecting plant sample, running the laboratory work, data analysis and drafted the paper. OPSF contributed in collecting plant sample, running the laboratory work. OCSDJ and JJS contributed to biological studies. MLH contributed to data analysis and drafted the paper. MAVS and EV designed the study, supervised the laboratory work and contributed to critical reading of the manuscript. All the authors have read the final manuscript and approved the submission.

Conflicts of interest

The authors declare no conflicts of interest.

* Corresponding author. E-mail:rafael.costa@ufba.br (R.S. Costa).

SCIMAGO INSTITUTIONS RANKINGS

Figures | Tables

Figures (4)
Tables (1)

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Fig. 1
Analytical and preparative HPLC chromatograms for RBE1 and RBE2 fractions. Analytical conditions: C₁₈ column (4.6 × 250 mm, 100 Å, 5 µm particle size, Kromasil^®), guard column (4.6 × 20 mm, 5 µm particle size), isocratic flow of MeOH:H₂O (1:1) at a rate of 0.6 ml/min, injection volume of 20 µl. Preparative conditions: C₁₈ column (21.2 × 250 mm, 5 µm, 100 Å), an isocratic flow MeOH:H₂O 1:1 and injection volume of 100 µl. The flow rate was 10 ml/min, DAD_254nm.

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Fig. 2
Analytical and preparative HPLC chromatograms for HR1 fraction. Analytical conditions: C₁₈ column (4.6 × 250 mm, 100 Å, 5 µm particle size, Kromasil^®), guard column (4.6 × 20 mm, 5 µm particle size), isocratic flow of MeOH:H₂O (1:1) at a rate of 0.6 ml/min, injection volume of 20 µl. Preparative conditions: C₁₈ column (21.2 × 250 mm, 5 µm, 100 Å), an isocratic flow MeOH:H₂O 1:1, injection volume of 100 µl at flow 6 ml/min, DAD_254nm.

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Fig. 3
Proliferation of Trypanosoma cruzi treated with 5,7,8-trimethoxycoumarin (1), braylin (6), syringaresinol (9) and γ-fagarine (12). Epimastigotes (5 × 10⁵ cells/ml) were incubated in different concentrations of the tested compounds at 26 ºC for 72 h and cell densities were determined by light microscopy. 20 µM benznidazole was employed as positive control. Statistical analysis was performed using One-way ANOVA and Tukey pos-test (*** p < 0.001, ** p < 0.01, * p < 0.05).

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Fig. 4
Proliferation of Leishmania amazonensis treated with 5,7,8-trimethoxycoumarin (1), braylin (6), syringaresinol (9) and γ-fagarine (12). Promastigotes (5 × 10⁵ cells/ml) were incubated in different concentrations of the tested compounds at 26 ºC for 72 h and cell densities were determined by light microscopy. Amphotericin (5 µM) was employed as positive control. Statistical analysis was performed using One-way ANOVA and Tukey pos-test (*** p < 0.001, ** p < 0.01, * p < 0.05).

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Table 1
Antileishmanial and antitrypanosomal activities of isolated compounds.

Fig. 1 Analytical and preparative HPLC chromatograms for RBE1 and RBE2 fractions. Analytical conditions: C₁₈ column (4.6 × 250 mm, 100 Å, 5 µm particle size, Kromasil^®), guard column (4.6 × 20 mm, 5 µm particle size), isocratic flow of MeOH:H₂O (1:1) at a rate of 0.6 ml/min, injection volume of 20 µl. Preparative conditions: C₁₈ column (21.2 × 250 mm, 5 µm, 100 Å), an isocratic flow MeOH:H₂O 1:1 and injection volume of 100 µl. The flow rate was 10 ml/min, DAD_254nm.

Fig. 2 Analytical and preparative HPLC chromatograms for HR1 fraction. Analytical conditions: C₁₈ column (4.6 × 250 mm, 100 Å, 5 µm particle size, Kromasil^®), guard column (4.6 × 20 mm, 5 µm particle size), isocratic flow of MeOH:H₂O (1:1) at a rate of 0.6 ml/min, injection volume of 20 µl. Preparative conditions: C₁₈ column (21.2 × 250 mm, 5 µm, 100 Å), an isocratic flow MeOH:H₂O 1:1, injection volume of 100 µl at flow 6 ml/min, DAD_254nm.

Fig. 3 Proliferation of Trypanosoma cruzi treated with 5,7,8-trimethoxycoumarin (1), braylin (6), syringaresinol (9) and γ-fagarine (12). Epimastigotes (5 × 10⁵ cells/ml) were incubated in different concentrations of the tested compounds at 26 ºC for 72 h and cell densities were determined by light microscopy. 20 µM benznidazole was employed as positive control. Statistical analysis was performed using One-way ANOVA and Tukey pos-test (* p < 0.001, p < 0.01, * p < 0.05).

Fig. 4 Proliferation of Leishmania amazonensis treated with 5,7,8-trimethoxycoumarin (1), braylin (6), syringaresinol (9) and γ-fagarine (12). Promastigotes (5 × 10⁵ cells/ml) were incubated in different concentrations of the tested compounds at 26 ºC for 72 h and cell densities were determined by light microscopy. Amphotericin (5 µM) was employed as positive control. Statistical analysis was performed using One-way ANOVA and Tukey pos-test (* p < 0.001, p < 0.01, * p < 0.05).

Fig. 3 Proliferation of Trypanosoma cruzi treated with 5,7,8-trimethoxycoumarin (1), braylin (6), syringaresinol (9) and γ-fagarine (12). Epimastigotes (5 × 10⁵ cells/ml) were incubated in different concentrations of the tested compounds at 26 ºC for 72 h and cell densities were determined by light microscopy. 20 µM benznidazole was employed as positive control. Statistical analysis was performed using One-way ANOVA and Tukey pos-test (* p < 0.001, p < 0.01, * p < 0.05).

Fig. 4 Proliferation of Leishmania amazonensis treated with 5,7,8-trimethoxycoumarin (1), braylin (6), syringaresinol (9) and γ-fagarine (12). Promastigotes (5 × 10⁵ cells/ml) were incubated in different concentrations of the tested compounds at 26 ºC for 72 h and cell densities were determined by light microscopy. Amphotericin (5 µM) was employed as positive control. Statistical analysis was performed using One-way ANOVA and Tukey pos-test (* p < 0.001, p < 0.01, * p < 0.05).

Table 1 Antileishmanial and antitrypanosomal activities of isolated compounds.

Compound	IC₅₀ ± SE (µM)
Compound	L. amazonensis (promastigotes)	T. cruzi (epimastigotes)
5,7,8-trimethoxycoumarin 1	57.7 ± 2.2	25.5 ± 0.3
Braylin 6	70.0 ± 1.2	59.8 ± 1.2
Syringoresinol 9	12.0 ± 1.2	7.6 ± 1.3
y-Fagarine 12	31.3 ± 1.4	33.4 ± 1.2

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Sociedade Brasileira de Farmacognosia Universidade Federal do Paraná, Laboratório de Farmacognosia, Rua Pref. Lothario Meissner, 632 - Jd. Botânico, 80210-170, Curitiba, PR, Brasil, Tel/FAX (41) 3360-4062 - Curitiba - PR - Brazil
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In vitro antileishmanial and antitrypanosomal activity of compounds isolated from the roots of Zanthoxylum tingoassuiba

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[1] Authors’ contributions

RSC contributed in collecting plant sample, running the laboratory work, data analysis and drafted the paper. OPSF contributed in collecting plant sample, running the laboratory work. OCSDJ and JJS contributed to biological studies. MLH contributed to data analysis and drafted the paper. MAVS and EV designed the study, supervised the laboratory work and contributed to critical reading of the manuscript. All the authors have read the final manuscript and approved the submission.