title: Aromatase and glycosyl transferase inhibiting acridone alkaloids from fruits of Cameroonian Zanthoxylum species.
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.
authors.affiliation: CSIR- Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India ; Babasaheb Bhimrao Ambedkar University, Lucknow 226025, India.
authors.forename: Vyry Na
authors.initials: VN
authors.lastname: Wouatsa
authors.affiliation: CSIR- Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India ; Chemical Sciences Division, CSIR- Central Institute of Medicinal and Aromatic Plants, Kuckrail Picnic Spot Road, P.O. CIMAP, Lucknow 226015, India.
authors.forename: Laxminarain
authors.initials: L
authors.lastname: Misra
authors.affiliation: CSIR- Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India.
authors.forename: Shiv
authors.initials: S
authors.lastname: Kumar
authors.affiliation: CSIR- Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India.
authors.forename: Om
authors.initials: O
authors.lastname: Prakash
authors.affiliation: CSIR- Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India.
authors.forename: Feroz
authors.initials: F
authors.lastname: Khan
authors.affiliation: Institute of Fisheries Sciences, University of Douala, Douala 24157, Cameroon.
authors.forename: Francois
authors.initials: F
authors.lastname: Tchoumbougnang
authors.affiliation: Babasaheb Bhimrao Ambedkar University, Lucknow 226025, India.
authors.forename: R Kumar
authors.initials: RK
authors.lastname: Venkatesh
keywords: Antibacterial; Cytotoxic activities; Molecular modeling; QSAR studies; Rutaceae; Structure elucidation; Z. leprieurii; Zanthacridones; Zanthoxylum zanthoxyloides