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Aromatase and glycosyl transferase inhibiting acridone alkaloids from fruits of Cameroonian Zanthoxylum species.

Wouatsa VN, Misra L, Kumar S, Prakash O, Khan F, Tchoumbougnang F, Venkatesh RK - Chem Cent J (2013)

Bottom 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: CSIR- Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India ; Babasaheb Bhimrao Ambedkar University, Lucknow 226025, India.

ABSTRACT

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 (IC50 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.

No MeSH data available.


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Structures of acridones 1- 10.
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Figure 1: Structures of acridones 1- 10.

Mentions: From the MeOH extract of the fruits of Z. zanthoxyloides, 6 new acridone alkaloids viz., 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) along with two known acridones, viz., helebelicine A (4) and 1-hydroxy-3-methoxy-10-methyl-9-acridone (5), have been isolated and identified (Figure 1). Compounds 8- 10 have a tetracyclic acridone carbon skeleton reported for the first time from Zanthoxylum spp. This novel acridone skeleton has, tentatively, been named as zanthacridone. From Z. leprieuri also, the new compound, 3-hydroxy-1,5,6-trimethoxy-9-acridone (1), was isolated along with three known acridones, namely, helebelicine A (4), 1,3-dihydroxy-4-methoxy-10-methyl-9-acridone (6) and tegerrardin A (7). All the compounds were Dragendorff positive and yellowish orange in color. The structures of the new compounds were elucidated mainly by UV, IR, NMR and MS spectroscopy (Additional file 1) and by comparison with the data already reported in the literature for acridone alkaloids [5,25-32].


Aromatase and glycosyl transferase inhibiting acridone alkaloids from fruits of Cameroonian Zanthoxylum species.

Wouatsa VN, Misra L, Kumar S, Prakash O, Khan F, Tchoumbougnang F, Venkatesh RK - Chem Cent J (2013)

Structures of acridones 1- 10.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750308&req=5

Figure 1: Structures of acridones 1- 10.
Mentions: From the MeOH extract of the fruits of Z. zanthoxyloides, 6 new acridone alkaloids viz., 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) along with two known acridones, viz., helebelicine A (4) and 1-hydroxy-3-methoxy-10-methyl-9-acridone (5), have been isolated and identified (Figure 1). Compounds 8- 10 have a tetracyclic acridone carbon skeleton reported for the first time from Zanthoxylum spp. This novel acridone skeleton has, tentatively, been named as zanthacridone. From Z. leprieuri also, the new compound, 3-hydroxy-1,5,6-trimethoxy-9-acridone (1), was isolated along with three known acridones, namely, helebelicine A (4), 1,3-dihydroxy-4-methoxy-10-methyl-9-acridone (6) and tegerrardin A (7). All the compounds were Dragendorff positive and yellowish orange in color. The structures of the new compounds were elucidated mainly by UV, IR, NMR and MS spectroscopy (Additional file 1) and by comparison with the data already reported in the literature for acridone alkaloids [5,25-32].

Bottom 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: CSIR- Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India ; Babasaheb Bhimrao Ambedkar University, Lucknow 226025, India.

ABSTRACT

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 (IC50 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.

No MeSH data available.


Related in: MedlinePlus