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

Chemistry Central Journal

Vyry NA Wouatsa¹  Laxminarain Misra⁴  Shiv Kumar³  Om Prakash³  Feroz Khan³  Francois Tchoumbougnang²  R Kumar Venkatesh¹ 

[1] Babasaheb Bhimrao Ambedkar University, Lucknow 226025, India

[2] Institute of Fisheries Sciences, University of Douala, Douala 24157, Cameroon

[3] CSIR- Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India

[4] Chemical Sciences Division, CSIR- Central Institute of Medicinal and Aromatic Plants, Kuckrail Picnic Spot Road, P.O. CIMAP, Lucknow 226015, India

关键词: QSAR studies;    Molecular modeling;    Cytotoxic activities;    Antibacterial;    Structure elucidation;    Zanthacridones;    Z. leprieurii;    Zanthoxylum zanthoxyloides;    Rutaceae;   

Others  :  787868
DOI  :  10.1186/1752-153X-7-125

 received in 2013-03-24, accepted in 2013-06-27,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Wouatsa et al.; licensee Chemistry Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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