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Aromatase and glycosyl transferase inhibiting acridone alkaloids from fruits of Cameroonian Zanthoxylum species
BACKGROUND: Zanthoxylum zanthoxyloides and Z. leprieurii fruits are commonly used in traditional system of medicine for diarrhea, pain, wound healing, etc. in Cameroon, Africa. Z. leprieurii fruits have been chemically studied for its bioactive compounds whereas the investigation on Z. zanthoxyloide...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3750308/ https://www.ncbi.nlm.nih.gov/pubmed/23866063 http://dx.doi.org/10.1186/1752-153X-7-125 |
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author | Wouatsa, Vyry NA Misra, Laxminarain Kumar, Shiv Prakash, Om Khan, Feroz Tchoumbougnang, Francois Venkatesh, R Kumar |
author_facet | Wouatsa, Vyry NA Misra, Laxminarain Kumar, Shiv Prakash, Om Khan, Feroz Tchoumbougnang, Francois Venkatesh, R Kumar |
author_sort | Wouatsa, Vyry NA |
collection | PubMed |
description | BACKGROUND: Zanthoxylum zanthoxyloides and Z. leprieurii fruits are commonly used in traditional system of medicine for diarrhea, pain, wound healing, etc. in Cameroon, Africa. Z. leprieurii fruits have been chemically studied for its bioactive compounds whereas the investigation on Z. zanthoxyloides fruits is lacking. RESULTS: After a detailed chemical analysis of the fruits of Z. leprieurii and Z. zanthoxyloides, a series of new acridone alkaloids, namely, 3-hydroxy-1,5,6-trimethoxy-9-acridone (1), 1,6-dihydroxy-3-methoxy-9-acridone (2), 3,4,5,7-tetrahydroxy-1-methoxy-10-methyl-9-acridone (3), 4-methoxyzanthacridone (8), 4-hydroxyzanthacridone (9), 4-hydroxyzanthacridone oxide (2,4’) (10) have been isolated. The known acridones which have been characterized are, helebelicine A (4), 1-hydroxy-3-methoxy-10-methyl-9-acridone (5), 1,3-dihydroxy-4-methoxy-10-methyl-9-acridone (6) and tegerrardin A (7). The in vitro antibacterial and cytotoxic screening of these acridones reveal that compound 3 has a moderate antibacterial activity (MIC 125 μg/mL) against Micrococcus luteus and Pseudomonas aeruginosa while compound 1 shows a moderate cytotoxic effect (IC(50) of 86 μM) against WRL-68 (liver cancer cell line). Furthermore, the molecular modeling of these acridones predicted the structural basis for their mode of action and binding affinity for aromatase, quinone reductase and WAAG, a glycosyltransferase involved in bacterial lipopolysaccharide synthesis. Computational approaches, quantitative SAR and modeling studies predicted that acridones 1, 2, 3, 4, 9 and 10 were the inhibitors of glycosyltransferase while 1, 8, 9 and 10, the inhibitors of aromatase. CONCLUSIONS: A total of 10 acridones have been isolated out of which 6 are new (1, 2, 3, 8, 9 and 10). Alkaloids 8, 9 and 10, having novel tetracyclic acridone structure with new carbon skeleton, have now been named as zanthacridone. The quantitative SAR and molecular modeling studies suggested that the compounds 1, 9 and 10 are inhibitors of both aromatase and glycosyltransferase. |
format | Online Article Text |
id | pubmed-3750308 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-37503082013-08-24 Aromatase and glycosyl transferase inhibiting acridone alkaloids from fruits of Cameroonian Zanthoxylum species Wouatsa, Vyry NA Misra, Laxminarain Kumar, Shiv Prakash, Om Khan, Feroz Tchoumbougnang, Francois Venkatesh, R Kumar Chem Cent J Research Article BACKGROUND: Zanthoxylum zanthoxyloides and Z. leprieurii fruits are commonly used in traditional system of medicine for diarrhea, pain, wound healing, etc. in Cameroon, Africa. Z. leprieurii fruits have been chemically studied for its bioactive compounds whereas the investigation on Z. zanthoxyloides fruits is lacking. RESULTS: After a detailed chemical analysis of the fruits of Z. leprieurii and Z. zanthoxyloides, a series of new acridone alkaloids, namely, 3-hydroxy-1,5,6-trimethoxy-9-acridone (1), 1,6-dihydroxy-3-methoxy-9-acridone (2), 3,4,5,7-tetrahydroxy-1-methoxy-10-methyl-9-acridone (3), 4-methoxyzanthacridone (8), 4-hydroxyzanthacridone (9), 4-hydroxyzanthacridone oxide (2,4’) (10) have been isolated. The known acridones which have been characterized are, helebelicine A (4), 1-hydroxy-3-methoxy-10-methyl-9-acridone (5), 1,3-dihydroxy-4-methoxy-10-methyl-9-acridone (6) and tegerrardin A (7). The in vitro antibacterial and cytotoxic screening of these acridones reveal that compound 3 has a moderate antibacterial activity (MIC 125 μg/mL) against Micrococcus luteus and Pseudomonas aeruginosa while compound 1 shows a moderate cytotoxic effect (IC(50) of 86 μM) against WRL-68 (liver cancer cell line). Furthermore, the molecular modeling of these acridones predicted the structural basis for their mode of action and binding affinity for aromatase, quinone reductase and WAAG, a glycosyltransferase involved in bacterial lipopolysaccharide synthesis. Computational approaches, quantitative SAR and modeling studies predicted that acridones 1, 2, 3, 4, 9 and 10 were the inhibitors of glycosyltransferase while 1, 8, 9 and 10, the inhibitors of aromatase. CONCLUSIONS: A total of 10 acridones have been isolated out of which 6 are new (1, 2, 3, 8, 9 and 10). Alkaloids 8, 9 and 10, having novel tetracyclic acridone structure with new carbon skeleton, have now been named as zanthacridone. The quantitative SAR and molecular modeling studies suggested that the compounds 1, 9 and 10 are inhibitors of both aromatase and glycosyltransferase. BioMed Central 2013-07-18 /pmc/articles/PMC3750308/ /pubmed/23866063 http://dx.doi.org/10.1186/1752-153X-7-125 Text en Copyright © 2013 Wouatsa et al.; licensee Chemistry Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Wouatsa, Vyry NA Misra, Laxminarain Kumar, Shiv Prakash, Om Khan, Feroz Tchoumbougnang, Francois Venkatesh, R Kumar Aromatase and glycosyl transferase inhibiting acridone alkaloids from fruits of Cameroonian Zanthoxylum species |
title | Aromatase and glycosyl transferase inhibiting acridone alkaloids from fruits of Cameroonian Zanthoxylum species |
title_full | Aromatase and glycosyl transferase inhibiting acridone alkaloids from fruits of Cameroonian Zanthoxylum species |
title_fullStr | Aromatase and glycosyl transferase inhibiting acridone alkaloids from fruits of Cameroonian Zanthoxylum species |
title_full_unstemmed | Aromatase and glycosyl transferase inhibiting acridone alkaloids from fruits of Cameroonian Zanthoxylum species |
title_short | Aromatase and glycosyl transferase inhibiting acridone alkaloids from fruits of Cameroonian Zanthoxylum species |
title_sort | aromatase and glycosyl transferase inhibiting acridone alkaloids from fruits of cameroonian zanthoxylum species |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3750308/ https://www.ncbi.nlm.nih.gov/pubmed/23866063 http://dx.doi.org/10.1186/1752-153X-7-125 |
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