title: Synthesis and molecular docking of N'-arylidene-5-(4-chlorophenyl)-1-(3,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carbohydrazides as novel hypoglycemic and antioxidant dual agents.
abstract: Herein, the design and synthesis of 10 novel N'-arylidene pyrazole-3-carbohydrazides are described. Compounds were pretended to act as dual agents against diabetes and oxidative stress, two correlated pathologies involved in metabolic syndrome development and progression. The antioxidant capacity was evaluated by means of DPPH and FRAP in vitro assays. It was found that compounds bearing a hydroxyl group at 4-position of the hydrazone moiety are potent antioxidant entities, being compound 3g (a syringaldehyde derivative) the most active compound. In addition, the in vivo hypoglycemic effect of the analogues was determined. With regard to the above, the cinnamaldehyde derivatives showed a scarce biological activity, while the 4-hydroxy analogues showed the higher glycemia reduction at 7h after administration. Interestingly, the most potent antioxidants 3b and 3g also were of the most active compounds in reducing the plasma glucose, reaching 80% of reduction in the case of 3g. Molecular docking binding poses conducted to a plausible interpretation of the biological outcomes and a possible interaction between a hydroxy group and Asn287 of CB1R was proposed as an important feature for enhancing the observed activity.
authors.affiliation: Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, México, DF 04510, Mexico. Electronic address: eduardo.hervaz@gmail.com.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Hernández-Vázquez
authors.affiliation: Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, México, DF 04510, Mexico.
authors.forename: Sandybel
authors.initials: S
authors.lastname: Salgado-Barrera
authors.affiliation: Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos 62209, Mexico.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Ramírez-Espinosa
authors.affiliation: Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos 62209, Mexico.
authors.forename: Samuel
authors.initials: S
authors.lastname: Estrada-Soto
authors.affiliation: Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, México, DF 04510, Mexico.
authors.forename: Francisco
authors.initials: F
authors.lastname: Hernández-Luis
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D054879:Halogenation; D006834:Hydrazines / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D007004:Hypoglycemic Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D062105:Molecular Docking Simulation; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism
chemical_list: D000975:Antioxidants; D001786:Blood Glucose; C543264:Cnr1 protein, rat; D006834:Hydrazines; D007004:Hypoglycemic Agents; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C019289:carbohydrazide
keywords: Antidiabetic effect; Antioxidant capacity; Cannabinoid receptor 1; Diarylpyrazole hybrids; Molecular docking