1070733-48-0Relevant academic research and scientific papers
In silico studies on 2,3-dihydro-1,5-benzothiazepines as cholinesterase inhibitors
Ansari, Farzana Latif,Kalsoom, Saima,Zaheer-Ul-Haq,Ali, Zahra,Jabeen, Farukh
, p. 2329 - 2339 (2012/11/07)
In vitro studies on cholinesterase inhibitory potential on the three sets of 2,3-dihydro-1,5-benzothiazepines have been carried out. The compounds in Set 1 were unsubstituted on ring A, while those in Sets 2 and 3 had a 2′- and 3′-hydoxy substituent, respectively, in ring A. These studies revealed that they are mixed inhibitors of both AChE and BChE as reflected from their IC50 values. It was further observed that 3′-hydroxy substituted benzothiazepines (Set 3) were found to have stronger affinity for both AChE and BChE compared with those of Sets 1 and 2. Moreover, all the compounds in Set 3 were found to be stronger BChE inhibitors than AChE. These experimental observations were rationalized by conducting in silico studies using molecular docking tool of Molecular Operating Environment (MOE) software, thereby, a good correlation was observed between IC50 values and their binding interactions within the enzyme active site. We have observed that these interactions were electrostatic and hydrophobic in nature besides hydrogen bonding. The high BChE inhibitory potential of 3′-hydroxy substituted benzothiazepines was found to be cumulative effect of hydrogen bonding and π-π interactions between the ligand and BChE. These findings may serve as a guideline for synthesizing more potent ChE inhibitors for the treatment of Alzheimer's disease and related dementias. Springer Science+Business Media, LLC 2011.
Solid-phase synthesis and biological evaluation of a parallel library of 2,3-dihydro-1,5-benzothiazepines
Ansari, Farzana Latif,Iftikhar, Fatima,Ihsan-ul-Haq,Mirza, Bushra,Baseer, Mohammad,Rashid, Umer
, p. 7691 - 7697 (2008/12/23)
Solid-phase synthesis of a parallel library of 3′-hydroxy-2,3-dihydrobenzothiazepines has been carried out through [4+3] annulation of α,β-unsaturated ketones with aminothiophenol, using Wang resin as solid support. The synthesized compounds were evaluated for their potential as antibacterial, tumor inhibitors as well as acetyl- and butyrylcholinesterase inhibitors. None of the compounds showed any significant antibacterial activity. However, quite a few compounds showed significant potential as crown gall tumor inhibitors. These results reflect a strong exploratory potential in search of new benzothiazepines as source of anticancer agents. The results of the inhibition of cholinesterase revealed that benzothiazepines have a greater potential as butyrylcholinesterase inhibitors as compared to acetylcholinesterase. Moreover, the substitution of hydroxy group at C-3 in ring A led to increased activity when compared to unsubstituted- and 2′-OH substituted benzothiazepines.
