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.