ABSTRACT
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.
Subject(s)
Acetylcholinesterase , Butyrylcholinesterase , Carbonic Anhydrase II , Carbonic Anhydrase I , Carbonic Anhydrase Inhibitors , Cholinesterase Inhibitors , Schiff Bases , Schiff Bases/pharmacology , Schiff Bases/chemistry , Schiff Bases/chemical synthesis , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/chemical synthesis , Cholinesterase Inhibitors/chemistry , Butyrylcholinesterase/metabolism , Acetylcholinesterase/metabolism , Humans , Carbonic Anhydrase II/antagonists & inhibitors , Carbonic Anhydrase II/metabolism , Carbonic Anhydrase Inhibitors/pharmacology , Carbonic Anhydrase Inhibitors/chemical synthesis , Carbonic Anhydrase Inhibitors/chemistry , Carbonic Anhydrase I/antagonists & inhibitors , Carbonic Anhydrase I/metabolism , Structure-Activity Relationship , Molecular Structure , Molecular Docking Simulation , Computer Simulation , Dose-Response Relationship, Drug , Models, MolecularABSTRACT
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.
Subject(s)
Biological Products/chemical synthesis , Biological Products/pharmacology , Carbonic Anhydrase Inhibitors/chemical synthesis , Carbonic Anhydrase Inhibitors/pharmacology , Carbonic Anhydrases/metabolism , Phenols/chemical synthesis , Phenols/pharmacology , Biological Products/chemistry , Bromobenzenes , Carbonic Anhydrase Inhibitors/chemistry , Chemistry Techniques, Synthetic , Esterases/metabolism , Humans , Isoenzymes/antagonists & inhibitors , Isoenzymes/metabolism , Phenols/chemistry , Phenylacetates/metabolism , PhloroglucinolABSTRACT
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.
Subject(s)
Bromine , Carbonic Anhydrase Inhibitors , Carbonic Anhydrases , Cyclohexanones , Phenols , Bromine/chemistry , Bromine/pharmacology , Carbonic Anhydrase Inhibitors/chemical synthesis , Carbonic Anhydrase Inhibitors/chemistry , Carbonic Anhydrase Inhibitors/pharmacology , Carbonic Anhydrases/chemistry , Crystallography, X-Ray , Cyclohexanones/chemical synthesis , Cyclohexanones/chemistry , Cyclohexanones/pharmacology , Enzyme Activation/drug effects , Humans , Models, Molecular , Molecular Structure , Phenols/chemical synthesis , Phenols/chemistry , Phenols/pharmacologyABSTRACT
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)°.
