Syntheses and Biological Activities of Chalcone and 1,5-Benzothiazepine Derivatives: Promising New Free-Radical Scavengers, and Esterase, Urease, and?-Glucosidase Inhibitors

Abstract

A series of 2,4-diaryl-2,3,4,5-tetrahydro- (36-40) and 2,4-diaryl-2,3-dihydro-1,5-benzothiazepines (25-35) have been synthesized from the corresponding chalcones 1-24. Both the benzothiazepines and chalcones were evaluated as DPPH free-radical scavengers and as inhibitors of cholinesterases, urease, and alpha-glucosidase. Compounds 2, 5, 6, 7, 10, 13, 18, 21, 36a, 37a, 37b, and 39a showed significant cholinesterase inhibiting activities. Among the 15 dihydro-1,5-benzothiazepines, 26, 32, and 35 exhibited significant radical-scavenging activities; and six tetrahydro-1,5-benzothiazepines (35, 36a, 36b, 37a, 37b, and 39a) were found to be inhibitors of AChE and BChE. Compounds 22, 25, 26, 33, 35, 36a, 37b, and 39a inhibited urease, and 25 and 27-31 were found to be potent inhibitors of alpha-glucosidase.

Structural insight into the inhibition of acetylcholinesterase by 2,3,4, 5-tetrahydro-1, 5-benzothiazepines

“…The synthesis of variety of chalcones 2, 3-dihydro-1, 5-benzothiazepines and their corresponding 2,3,4,5-tetrahydrobenzothiazepines has earlier been reported [16] and studies on their AChE and BChE inhibitory potential were also carried out. However, it was found that only 2,3,4,5-tetrahydrobenzothiazepines showed a significant AChE inhibition; Therefore, it was considered worthwhile to have a deeper insight in the mechanism of interaction of these benzothiazepines with AChE by kinetics and molecular docking studies.…”

“…The inhibition kinetics, pharmacological profiles, molecular docking, 3D-QSAR (CoMFA and CoMSIA) studies have also been conducted for a good number of compounds [11][12][13][14][15]. Continuing our on going search for new inhibitors of therapeutically significant enzymes through highthroughput screening assays, we recently synthesized benzothiazepines 1-3, with valuable AChE inhibitory potential [16].…”

Microwave assisted synthesis, antibacterial activity against Bordetella bronchiseptica of a library of 3΄-hydroxyaryl and heteroaryl chalcones and molecular descriptors-based SAR

“…3-bromo and 3-chloro-have been found to possess high values of hydrophobicity constant (π), octanol-water partition coefficient (log P) and molar volume (Vm) with the exception of methoxy substituted chalcones. Moreover, the manifested bactericidal effect was also found to be facilitated by the presence of electron acceptors on the phenyl ring of chalcones of Set 1, the only exception being the nitro group which irrespective of its position on the phenyl ring suppressed the activity of all three regioisomeric chalcones (18)(19)(20). It may therefore be implied that the lipophilicity of the compounds appeared to be the main predictor of bactericidal activity.…”

“…We have reported earlier the design and synthesis of a 120-member library and its screening against a number of bacterial strains and the lead structure was identified through deconvolution based on positional scanning protocol. 18 Prompted by the findings and in continuation to our interest in the synthesis of biodynamic chalcones, 19,20 we synthesized a parallel library of 3-hydroxy-aryl and heteroaryl chalcones in order to study their bactericidal potential against B. bronchiseptica. Although we tested these compounds also against a number of other gram-positive and gram-negative bacterial strain namely, Micrococcus leuteus ATCC10240, Pseudomonas picketti ATCC 49129, Escherichia coli ATCC 15224, Enterobacter aerogenes ATCC 13048, and Salmonella setubal ATCC 19196, however, with the exception of B. bronchiseptica all the compounds were found to be generally inactive against these strains.…”

“…The reaction time under microwave irradiation varied from 30 to 180 sec. However, chalcones 2-4, 9 and all heteroaryl chalcones (24-33) were synthesized by conventional method 19) as the reaction mixture decomposed on irradiation. Table 1 while a graphical representation of the same data is given in Figure 1.…”