Journal of Pharmaceutical and Biomedical Sciences

Synthesis of Nitrate Derivatives of Apocynin Dimer Analogue

Gaofang Wang, Yang Ou, Zhijian Zhang, Jie Jiang | Vol 08 | Issue 04 | Pp:56-62.

Abstract


Acute lung injury (ALI) is a mortal disease without satisfactory therapy and poor prognosis. It is believed that lung injury relates much to excessive production of reactive oxygen species (ROS) and a host of pro-inflammatory factors. Anti-oxidative and anti-inflammatory agents may be potential for ALI treatment. Factors, such as ROS, TNF-?, and nitric oxide
(NO) play important role in oxidative stress and inflammation process of ALI. Apocynin, a natural phenolic antioxidant, demonstrated activity against oxidative stress and inflammation.

Apocynin was reported to turn into dimer or trimer derivatives to exert action. Our previous work showed that apocynin dimer analogue, JJA-D0, reduced ROS level and expression of TNF-? and NADPH oxidase. In this work, NO donor of nitrate was conjugated with JJA-D0 by its phenolic groups to synthesize four nitrate derivatives, which were expected to obtain enhanced anti-oxidative and anti-inflammatory activity through increasing the action of modulating NO level. The four derivatives, JJA-D1–JJA-D4, were synthesized under moderate condition with a yield around 10–40% calculated by starting material of 5-acetyl-2-hydroxy-3-methoxybenzaldehyde (Apo-CHO) or 1-(3-amino-4-hydroxy-5-methoxyphenyl) ethanone (Apo-NH2). The docking of the derivatives with 1K4U subsection of human neutrophil NADPH oxidase system was preliminarily investigated
using Goldscore function available in GOLD 5.0.1 program. The results demonstrated that the derivatives got higher score (>44) than apocynin (25.8647), which indicated a possible stronger binding with NADPH oxidase.


Keywords


apocynin dimer analogue, nitrate derivative, synthesis

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