Protein tyrosine phosphatase 1B inhibitory activity of compounds from Justicia spicigera (Acanthaceae)

• Published in: Phytochemistry (Oxford) 2022-11, Vol.203, p.113410-113410, Article 113410
• Main Authors: Pérez-Vásquez, Araceli, Díaz-Rojas, Miriam, Castillejos-Ramírez, Erika V., Pérez-Esquivel, Alejandra, Montaño-Cruz, Yullet, Rivero-Cruz, Isabel, Torres-Colín, Rafael, González-Andrade, Martin, Rodríguez-Sotres, Rogelio, Gutiérrez-González, José Alberto, Madariaga-Mazón, Abraham, Mata, Rachel
• Format: Article
• Language: English
• Subjects: 2,5-Dimethoxy-p-benzoquinone; 2-N-(p-coumaroyl)-3H-phenoxazin-3-one; 3″-O-Acetyl-kaempferitrin; Acanthaceae; J. spicigera; Kaempferitrin; Perisbivalvine B; Protein tyrosine phosphatase 1B
• ISSN: 0031-9422; 1873-3700
• DOI: 10.1016/j.phytochem.2022.113410

An infusion from the aerial parts of Justicia spicigera Schltdl., an herb commonly used to treat diabetes, inhibited the activity of protein tyrosine phosphatase 1B (PTP1B). Two undescribed compounds, 2-N-(p-coumaroyl)-3H-phenoxazin-3-one, and 3″-O-acetyl-kaempferitrin, along with kaempferitrin, kaempferol 7-O-α-L-rhamnopyranoside, perisbivalvine B and 2,5-dimethoxy-p-benzoquinone were isolated from the active extract. Their structures were elucidated by a combination of spectroscopic and spectrometric methods. The isolates were evaluated for their inhibitory activity against PTP1B; the most active compounds were 2-N-(p-coumaroyl)-3H-phenoxazin-3-one, and perisbivalvine B with IC50 values of 159.1 ± 0.02 μM and 106.6 ± 0.01 μM, respectively. However, perisbivalvine B was unstable. Kinetic analysis of 2-N-(p-coumaroyl)-3H-phenoxazin-3-one and 2,5-dimethoxy-p-benzoquinone (obtained in good amounts) indicated that both compounds behaved as parabolic competitive inhibitors and bind to the enzyme forming complexes with 1:1 and 1:2 stoichiometry. Docking of 2-N-(p-coumaroyl)-3H-phenoxazin-3-one and 2,5-dimethoxy-p-benzoquinone to PTP1B1-400 predicted a good affinity of these compounds for PTP1B catalytic site and demonstrated that the binding of a second ligand is sterically possible. The 1:2 complex was also supported by the second docking analysis, which predicted an important contribution of π-stacking interactions to the stability of these 1:2 complexes. Finally, an UHPLC-MS method was developed and validated to quantify the content of kaempferitrin in the infusion of the plant. [Display omitted] •Justicia spicigera Schltdl. contains phenoxazin-3-ones.•2-N-(p-Coumaroyl)-3H-phenoxazin-3-one competitively inhibits PTP1B.•This the first report of phenoxazin-3-ones in the genus Justicia.•2-N-(p-Coumaroyl)-3H-phenoxazin-3-one is a dyeing substance.•Docking of 2-N-(p-coumaroyl)-3H-phenoxazin-3-one predicted a good affinity for PTP1B catalytic site.