RESUMEN
This study reports a rapid and efficient synthesis of four novel aryl Schiff base derivatives. Biological activity and molecular modeling studies were conducted to evaluate the inhibitory effects of these compounds on human carbonic anhydrases (hCA) and cholinesterases. The results indicate that the triazole-ring-containing compounds have strong inhibitory effects on hCA I, hCA II, acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) targets. Besides comparing the Schiff bases synthesized in our study to reference molecules, we conducted in silico investigations to examine how these compounds interact with their targets. Our studies revealed that these compounds can occupy binding sites and establish interactions with crucial residues, thus inhibiting the functions of the targets. These findings have significant implications as they can be utilized to develop more potent compounds for treating the diseases that these target proteins play crucial roles in or to obtain drug precursors with enhanced efficacy.
Asunto(s)
Acetilcolinesterasa , Butirilcolinesterasa , Anhidrasa Carbónica II , Anhidrasa Carbónica I , Inhibidores de Anhidrasa Carbónica , Inhibidores de la Colinesterasa , Bases de Schiff , Bases de Schiff/farmacología , Bases de Schiff/química , Bases de Schiff/síntesis química , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/síntesis química , Inhibidores de la Colinesterasa/química , Butirilcolinesterasa/metabolismo , Acetilcolinesterasa/metabolismo , Humanos , Anhidrasa Carbónica II/antagonistas & inhibidores , Anhidrasa Carbónica II/metabolismo , Inhibidores de Anhidrasa Carbónica/farmacología , Inhibidores de Anhidrasa Carbónica/síntesis química , Inhibidores de Anhidrasa Carbónica/química , Anhidrasa Carbónica I/antagonistas & inhibidores , Anhidrasa Carbónica I/metabolismo , Relación Estructura-Actividad , Estructura Molecular , Simulación del Acoplamiento Molecular , Simulación por Computador , Relación Dosis-Respuesta a Droga , Modelos MolecularesRESUMEN
A series of bisphenol, bromophenol, and methoxyphenol derivatives (2-24) including the natural bromophenols vidalol B, 3,4,6-tribromo-5-(2,5-dibromo-3,4-dihydroxybenzyl)benzene-1,2-diol (2) and 5,5'-methylenebis(3,4,6-tribromo-benzene-1,2-diol) (3) were prepared. In the current study, inhibition of four human carbonic anhydrase (hCA, EC 4.2.1.1) isozymes, I, II, IV, and VI, with these compounds 2-24 was investigated. The compounds 2-24 were found to be promising carbonic anhydrase inhibitors, some of which showed interesting inhibitory activities. Some of the compounds investigated here showed effective hCA inhibitory activity, and might be used as leads for generating novel carbonic anhydrase inhibitors which are valuable drug candidates for the treatment of glaucoma, epilepsy, gastric and duodenal ulcers, neurological disorders, and osteoporosis.
Asunto(s)
Productos Biológicos/síntesis química , Productos Biológicos/farmacología , Inhibidores de Anhidrasa Carbónica/síntesis química , Inhibidores de Anhidrasa Carbónica/farmacología , Anhidrasas Carbónicas/metabolismo , Fenoles/síntesis química , Fenoles/farmacología , Productos Biológicos/química , Bromobencenos , Inhibidores de Anhidrasa Carbónica/química , Técnicas de Química Sintética , Esterasas/metabolismo , Humanos , Isoenzimas/antagonistas & inhibidores , Isoenzimas/metabolismo , Fenoles/química , Fenilacetatos/metabolismo , FloroglucinolRESUMEN
The Naturally occurring novel cyclohexanonyl bromophenol 2(R)-2-(2,3,6-tribromo-4,5-dihydroxybenzyl)cyclohexanone (4) was synthesized as a racemic compound. Cyclohexylphenyl methane derivatives (10-17) with Br, OMe, CO, and OH were also obtained. Inhibition of four human carbonic anhydrase (hCA, EC 4.2.1.1) isozymes I, II, IV, and VI, with compounds 2-4, 8, and 10-26 was investigated. These compounds were found to be promising carbonic anhydrase inhibitors and some of them showed interesting inhibitory activity. Some of the compounds investigated here showed effective hCA inhibitory activity, and might be used as leads for generating novel carbonic anhydrase inhibitors which are valuable drug candidates for the treatment of glaucoma, epilepsy, gastric and duodenal ulcers, neurological disorders, and osteoporosis.
Asunto(s)
Bromo , Inhibidores de Anhidrasa Carbónica , Anhidrasas Carbónicas , Ciclohexanonas , Fenoles , Bromo/química , Bromo/farmacología , Inhibidores de Anhidrasa Carbónica/síntesis química , Inhibidores de Anhidrasa Carbónica/química , Inhibidores de Anhidrasa Carbónica/farmacología , Anhidrasas Carbónicas/química , Cristalografía por Rayos X , Ciclohexanonas/síntesis química , Ciclohexanonas/química , Ciclohexanonas/farmacología , Activación Enzimática/efectos de los fármacos , Humanos , Modelos Moleculares , Estructura Molecular , Fenoles/síntesis química , Fenoles/química , Fenoles/farmacologíaRESUMEN
The mol-ecule of the title compound, C(26)H(26)Br(4)O(6), is located around a crystallographic inversion center. The dihedral angle between the central benzene ring and the outer benzene ring is 89.26â (1)°.