Background: Zanthoxylum zanthoxyloidesandZ. leprieuriifruits are commonly used in traditional system of medicine for diarrhea, pain, wound healing, etc. in Cameroon, Africa.Z. leprieuriifruits have been chemically studied for its bioactive compounds whereas the investigation onZ. zanthoxyloidesfruits is lacking.Results: After a detailed chemical analysis of the fruits ofZ. leprieuriiandZ. 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 vitroantibacterial and cytotoxic screening of these acridones reveal that compound3has a moderate antibacterial activity (MIC 125 μg/mL) againstMicrococcus luteusandPseudomonas aeruginosawhile compound1shows a moderate cytotoxic effect (IC₅₀of 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 acridones1, 2, 3, 4, 9and10were the inhibitors of glycosyltransferase while1,8, 9and10,the inhibitors of aromatase.Conclusions: A total of 10 acridones have been isolated out of which 6 are new (1,2,3,8,9and10). Alkaloids8,9and10, 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 compounds1,9and10are inhibitors of both aromatase and glycosyltransferase.

Crosstalk of signaling pathways plays crucial roles in cell fate determination, cell differentiation and proliferation. Both BMP-4/Smad-1 and FGF/Xbra signaling induce the expression of PV.1, leading to neural inhibition. However, BMP-4/Smad-1 and FGF/Xbra signaling crosstalk in the regulation of PV.1 transcription is still largely unknown. In this study, Smad-1 and Xbra physically interacted and regulated the PV.1 transcriptional activation in a synergistic manner. Xbra and Smad-1 directly bound within the proximal region of the PV.1 promoter and cooperatively enhanced the binding of an interacting partner within the promoter. Maximum cooperation was achieved in the presence of intact DNA binding sites of both Smad-1 and Xbra. Collectively, BMP-4/Smad-1 and FGF/Xbra signal crosstalk was required to activate the PV.1 transcription, synergistically. Suggesting that crosstalk of BMP-4 and FGF signaling facilitates the fine-tuning regulation of PV.1 transcription to inhibit neurogenesis during embryonic development of Xenopus. Summary statement: FGF/Xbra positively regulates the PV.1 expression in the Xenopus via an unknown mechanism. Our study shows that both BMP-4/Smad-1 and FGF/Xbra exhibits a signaling crosstalk to regulate PV.1 transcription activation, promoting to ectoderm and mesoderm formation and inhibiting the early neurogenesis in Xenopus.