Easy and rapid preparation of benzoylhydrazides and their diazene derivatives as inhibitors of 15-lipoxygenase.
Two series of diaza derivatives were prepared by solvent-free condensation of benzoic acid and 4-substituted phenylhydrazines in order to obtain phenylhydrazides (HYD series) and, by oxidation of these compounds, the corresponding benzoyldiazenes (DIA series). Both sets were evaluated as inhibitors of soybean 15-lipoxygenase activity and antioxidant capability in the FRAP and CUPRAC assays. The most potent inhibitors of both series exhibited IC50values in the low micromolar range. Kinetic studies showed that at least the more active compounds were competitive inhibitors. Docking results indicated that the most potent inhibitor interacts strongly with Ile-839 and iron in the active site.
Departamento de Química, Facultad de Ciencias, Universidad de Chile, Casilla 653, Santiago, Chile; Facultad de Química y Biología, Universidad de Santiago de Chile, Casilla 40, correo 33, Santiago, Chile. Electronic address: cristian.tirapeguic@usach.cl.
Cristian
C
Tirapegui
Departamento de Química, Facultad de Ciencias, Universidad de Chile, Casilla 653, Santiago, Chile.
Williams
W
Acevedo-Fuentes
Facultad de Química y Biología, Universidad de Santiago de Chile, Casilla 40, correo 33, Santiago, Chile.
Pablo
P
Dahech
Facultad de Química y Biología, Universidad de Santiago de Chile, Casilla 40, correo 33, Santiago, Chile.
Claudia
C
Torrent
Facultad de Química y Biología, Universidad de Santiago de Chile, Casilla 40, correo 33, Santiago, Chile.
Pablo
P
Barrias
Relativistic Molecular Physics (ReMoPh) Group, Ph.D. Program in Molecular, Physical Chemistry, Universidad Andrés Bello, Av. República 275, Santiago 8370146, Chile; Universidad Tecnológica de Chile INACAP, Chile.
Macarena
M
Rojas-Poblete
Facultad de Química y Biología, Universidad de Santiago de Chile, Casilla 40, correo 33, Santiago, Chile.
Carolina
C
Mascayano
D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism*; D001565:Benzoates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D060326:Chemistry Techniques, Synthetic / Q000191:economics / Q000379:methods; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D007094:Imides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D062105:Molecular Docking Simulation; D010084:Oxidation-Reduction; D013025:Glycine max / Q000187:drug effects / Q000201:enzymology; D013329:Structure-Activity Relationship
D000975:Antioxidants; D001565:Benzoates; D006834:Hydrazines; D007094:Imides; D016859:Lipoxygenase Inhibitors; D001093:Arachidonate 15-Lipoxygenase; C038867:diazene
15-Lipoxygenase inhibition; Antioxidant capability; Benzoyldiazene; Lipophilicity; Phenylhydrazides