title: 1,5-Diarylpyrazole and vanillin hybrids: Synthesis, biological activity and DFT studies.
abstract: Herein, we report the design and synthesis of 13 diarylpyrazole hybrids with vanillin constructed as dual compounds against oxidative stress and diabetes. Compounds were tested in two different antioxidant assays. It was found that all compounds showed an important antioxidant activity in both DPPH and ORAC models and the activity was even more remarkable than vanillin. In addition, the hypoglycemic effect of compounds 1, 2, 4 and 12 was evaluated. Interestingly, compound 1 had the most potent hypoglycemic effect with a glycemia reduction of 71%, which was higher than rimonabant. Finally, a DFT study to propose a reasonable antioxidant mechanism is detailed. Both thermodynamic and kinetic studies indicated that the most feasible mechanism consists in the HAT abstraction of the phenolic hydrogen due to the formation of an stable transition state through the most rapid and exergonic path, while the SPLET mechanism is the most significant at higher pH values.
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 Física y Química Teórica, Universidad Nacional Autónoma de México, México, DF 04510, Mexico.
authors.forename: Romina
authors.initials: R
authors.lastname: Castañeda-Arriaga
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 Química, Departamento de Biología, Universidad Nacional Autónoma de México, México, DF 04510, Mexico.
authors.forename: Omar Noel
authors.initials: ON
authors.lastname: Medina-Campos
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
authors.affiliation: Facultad de Química, Departamento de Biología, Universidad Nacional Autónoma de México, México, DF 04510, Mexico.
authors.forename: José Pedraza
authors.initials: JP
authors.lastname: Chaverri
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
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001547:Benzaldehydes / Q000737:chemistry / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D007003:Hypoglycemia / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D018384:Oxidative Stress / Q000187:drug effects; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology*; D011789:Quantum Theory; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D001547:Benzaldehydes; D007004:Hypoglycemic Agents; D011720:Pyrazoles; C100058:vanillin
keywords: Antioxidant capacity; DFT calculations; Diarylpyrazole hybrids; Vanillin