ABSTRACT
A series of benzene sulfonamides 15-26 were synthesized and determined for their in vitro and in silico inhibitory profiles toward acetylcholinesterase (AChE) and carbonic anhydrases (CAs). Commercially available 3,4-dimethoxytoluene was reacted with chlorosulfonic acid to furnish benzene sulfonyl chloride derivatives. The reaction of substituted benzene sulfonyl chloride with some amines also including (±)-α-amino acid methyl esters afforded a series of novel benzene sulfonamides. In this study, the enzyme inhibition abilities of these compounds were evaluated against AChE and CAs. They exhibited a highly potent inhibition ability on AChE and -CAs (Ki values are in the range of 28.11 ± 4.55 nM and 145.52 ± 28.68 nM for AChE, 39.20 ± 2.10 nM to 131.54 ± 12.82 nM for CA I, and 50.96 ± 9.83 nM and 147.94 ± 18.75 nM for CA II). The present newly synthesized novel benzene sulfonamides displayed efficient inhibitory profiles against AChE and CAs, and it is anticipated that they may emerge as lead molecules for some diseases including glaucoma, epilepsy, and Alzheimer's disease.
Subject(s)
Acetylcholinesterase , Carbonic Anhydrase Inhibitors , Cholinesterase Inhibitors , Sulfonamides , Carbonic Anhydrase Inhibitors/pharmacology , Carbonic Anhydrase Inhibitors/chemical synthesis , Carbonic Anhydrase Inhibitors/chemistry , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/chemical synthesis , Cholinesterase Inhibitors/chemistry , Sulfonamides/pharmacology , Sulfonamides/chemistry , Sulfonamides/chemical synthesis , Acetylcholinesterase/metabolism , Structure-Activity Relationship , Molecular Structure , Molecular Docking Simulation , Humans , Carbonic Anhydrases/metabolism , Dose-Response Relationship, Drug , Benzenesulfonamides , Benzene/chemistryABSTRACT
The redetermination of the structure of the title compound, [Fe(C15H12N4)2](ClO4)2, (I), confirms the structure previously reported [Kucharski et al. (1978a â¸). Aust. J. Chem. 31, 53-56], but models the perchlorate over four sets of atomic sites, rather than using just one set of sites as in the original report. The supra-molecular assembly, not reported previously, takes the form of a complex three-dimensional framework built from C-Hâ¯O hydrogen bonds. The isotypic nickel(II) analogue, [Ni(C15H12N4)2](ClO4)2, (III), has been refined using the original data set [Wang et al. (2011 â¸). Acta Cryst. E67, m78], again using a four-component disorder model for the anion, rather than a two-component model as in the original report, leading to more satisfactory Cl-O distances and O-Cl-O angles.
