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Benzylated Dihydroflavones and Isoquinoline-Derived Alkaloids from the Bark of Diclinanona calycina (Annonaceae) and Their Cytotoxicities

Diclinanona calycina R. E. Fries popularly known as “envira”, is a species of the Annonaceae family endemic to Brazil. In our ongoing search for bioactive compounds from Annonaceae Amazon plants, the bark of D. calycina was investigated by classical chromatography techniques that yielded thirteen co...

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Autores principales: Costa, Emmanoel V., Soares, Liviane do N., Chaar, Jamal da Silva, Silva, Valdenizia R., Santos, Luciano de S., Koolen, Hector H. F., da Silva, Felipe M. A., Tavares, Josean F., Zengin, Gokhan, Soares, Milena B. P., Bezerra, Daniel P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235387/
https://www.ncbi.nlm.nih.gov/pubmed/34207059
http://dx.doi.org/10.3390/molecules26123714
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author Costa, Emmanoel V.
Soares, Liviane do N.
Chaar, Jamal da Silva
Silva, Valdenizia R.
Santos, Luciano de S.
Koolen, Hector H. F.
da Silva, Felipe M. A.
Tavares, Josean F.
Zengin, Gokhan
Soares, Milena B. P.
Bezerra, Daniel P.
author_facet Costa, Emmanoel V.
Soares, Liviane do N.
Chaar, Jamal da Silva
Silva, Valdenizia R.
Santos, Luciano de S.
Koolen, Hector H. F.
da Silva, Felipe M. A.
Tavares, Josean F.
Zengin, Gokhan
Soares, Milena B. P.
Bezerra, Daniel P.
author_sort Costa, Emmanoel V.
collection PubMed
description Diclinanona calycina R. E. Fries popularly known as “envira”, is a species of the Annonaceae family endemic to Brazil. In our ongoing search for bioactive compounds from Annonaceae Amazon plants, the bark of D. calycina was investigated by classical chromatography techniques that yielded thirteen compounds (alkaloids and flavonoids) described for the first time in D. calycina as well as in the genus Diclinanona. The structure of these isolated compounds were established by extensive analysis using 1D/2D-NMR spectroscopy in combination with MS. The isolated alkaloids were identified as belonging to the subclasses: simple isoquinoline, thalifoline (1); aporphine, anonaine (2); oxoaporphine, liriodenine (3); benzyltetrahydroisoquinolines, (S)-(+)-reticuline (4); dehydro-oxonorreticuline (3,4-dihydro-7-hydroxy-6-methoxy-1-isoquinolinyl)(3-hydroxy-4-methoxyphenyl)-methanone) (5); (+)-1S,2R-reticuline N(β)-oxide (6); and (+)-1S,2S-reticuline N(α)-oxide (7); tetrahydroprotoberberine, coreximine (8); and pavine, bisnorargemonine (9). While the flavonoids belong to the benzylated dihydroflavones, isochamanetin (10), dichamanetin (11), and a mixture of uvarinol (12) and isouvarinol (13). Compound 5 is described for the first time in the literature as a natural product. The cytotoxic activity of the main isolated compounds was evaluated against cancer and non-cancerous cell lines. Among the tested compounds, the most promising results were found for the benzylated dihydroflavones dichamanetin (10), and the mixture of uvarinol (12) and isouvarinol (13), which presented moderate cytotoxic activity against the tested cancer cell lines (<20.0 µg·mL(−1)) and low cytotoxicity against the non-cancerous cell line MRC-5 (>25.0 µg·mL(−1)). Dichamanetin (11) showed cytotoxic activity against HL-60 and HCT116 with IC(50) values of 15.78 µg·mL(−1) (33.70 µmol·L(−1)) and 18.99 µg·mL(−1) (40.56 µmol·L(−1)), respectively while the mixture of uvarinol (12) and isouvarinol (13) demonstrated cytotoxic activity against HL-60, with an IC(50) value of 9.74 µg·mL(−1), and HCT116, with an IC(50) value of 17.31 µg·mL(−1). These cytotoxic activities can be attributed to the presence of one or more hydroxybenzyl groups present in these molecules as well as the position in which these groups are linked. The cytotoxic activities of reticuline, anonaine and liriodenine have been previously established, with liriodenine being the most potent compound.
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spelling pubmed-82353872021-06-27 Benzylated Dihydroflavones and Isoquinoline-Derived Alkaloids from the Bark of Diclinanona calycina (Annonaceae) and Their Cytotoxicities Costa, Emmanoel V. Soares, Liviane do N. Chaar, Jamal da Silva Silva, Valdenizia R. Santos, Luciano de S. Koolen, Hector H. F. da Silva, Felipe M. A. Tavares, Josean F. Zengin, Gokhan Soares, Milena B. P. Bezerra, Daniel P. Molecules Article Diclinanona calycina R. E. Fries popularly known as “envira”, is a species of the Annonaceae family endemic to Brazil. In our ongoing search for bioactive compounds from Annonaceae Amazon plants, the bark of D. calycina was investigated by classical chromatography techniques that yielded thirteen compounds (alkaloids and flavonoids) described for the first time in D. calycina as well as in the genus Diclinanona. The structure of these isolated compounds were established by extensive analysis using 1D/2D-NMR spectroscopy in combination with MS. The isolated alkaloids were identified as belonging to the subclasses: simple isoquinoline, thalifoline (1); aporphine, anonaine (2); oxoaporphine, liriodenine (3); benzyltetrahydroisoquinolines, (S)-(+)-reticuline (4); dehydro-oxonorreticuline (3,4-dihydro-7-hydroxy-6-methoxy-1-isoquinolinyl)(3-hydroxy-4-methoxyphenyl)-methanone) (5); (+)-1S,2R-reticuline N(β)-oxide (6); and (+)-1S,2S-reticuline N(α)-oxide (7); tetrahydroprotoberberine, coreximine (8); and pavine, bisnorargemonine (9). While the flavonoids belong to the benzylated dihydroflavones, isochamanetin (10), dichamanetin (11), and a mixture of uvarinol (12) and isouvarinol (13). Compound 5 is described for the first time in the literature as a natural product. The cytotoxic activity of the main isolated compounds was evaluated against cancer and non-cancerous cell lines. Among the tested compounds, the most promising results were found for the benzylated dihydroflavones dichamanetin (10), and the mixture of uvarinol (12) and isouvarinol (13), which presented moderate cytotoxic activity against the tested cancer cell lines (<20.0 µg·mL(−1)) and low cytotoxicity against the non-cancerous cell line MRC-5 (>25.0 µg·mL(−1)). Dichamanetin (11) showed cytotoxic activity against HL-60 and HCT116 with IC(50) values of 15.78 µg·mL(−1) (33.70 µmol·L(−1)) and 18.99 µg·mL(−1) (40.56 µmol·L(−1)), respectively while the mixture of uvarinol (12) and isouvarinol (13) demonstrated cytotoxic activity against HL-60, with an IC(50) value of 9.74 µg·mL(−1), and HCT116, with an IC(50) value of 17.31 µg·mL(−1). These cytotoxic activities can be attributed to the presence of one or more hydroxybenzyl groups present in these molecules as well as the position in which these groups are linked. The cytotoxic activities of reticuline, anonaine and liriodenine have been previously established, with liriodenine being the most potent compound. MDPI 2021-06-18 /pmc/articles/PMC8235387/ /pubmed/34207059 http://dx.doi.org/10.3390/molecules26123714 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Costa, Emmanoel V.
Soares, Liviane do N.
Chaar, Jamal da Silva
Silva, Valdenizia R.
Santos, Luciano de S.
Koolen, Hector H. F.
da Silva, Felipe M. A.
Tavares, Josean F.
Zengin, Gokhan
Soares, Milena B. P.
Bezerra, Daniel P.
Benzylated Dihydroflavones and Isoquinoline-Derived Alkaloids from the Bark of Diclinanona calycina (Annonaceae) and Their Cytotoxicities
title Benzylated Dihydroflavones and Isoquinoline-Derived Alkaloids from the Bark of Diclinanona calycina (Annonaceae) and Their Cytotoxicities
title_full Benzylated Dihydroflavones and Isoquinoline-Derived Alkaloids from the Bark of Diclinanona calycina (Annonaceae) and Their Cytotoxicities
title_fullStr Benzylated Dihydroflavones and Isoquinoline-Derived Alkaloids from the Bark of Diclinanona calycina (Annonaceae) and Their Cytotoxicities
title_full_unstemmed Benzylated Dihydroflavones and Isoquinoline-Derived Alkaloids from the Bark of Diclinanona calycina (Annonaceae) and Their Cytotoxicities
title_short Benzylated Dihydroflavones and Isoquinoline-Derived Alkaloids from the Bark of Diclinanona calycina (Annonaceae) and Their Cytotoxicities
title_sort benzylated dihydroflavones and isoquinoline-derived alkaloids from the bark of diclinanona calycina (annonaceae) and their cytotoxicities
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235387/
https://www.ncbi.nlm.nih.gov/pubmed/34207059
http://dx.doi.org/10.3390/molecules26123714
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