Synthesis and anticholinesterase activities of novel 1,3,4-thiadiazole based compounds

Skrzypek, Alicja; Matysiak, Joanna; Karpińska, Monika; Niewiadomy, Andrzej

doi:10.3109/14756366.2012.688041

Cited by 30 publications

(14 citation statements)

References 20 publications

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“…Benzimidazole derivatives are also known as β-glucuronidase [16,17], α-glucosidase [18,19], urease [20], and α-amylase enzymes inhibitors [21]. Molecular modeling studies for 5-aryl-4-(1,3,4-thiadiazol-2-yl)benzene-1,3-diols obtained by us indicated a network of essential bonds between the -OH groups of the benzenediol ring and the residues of amino acid AChE in the active site which results in a significant inhibitory effect against AChE [22,23]. Some of them also displayed neuroprotective properties [24].…”

Section: Introductionmentioning

confidence: 99%

Biological Evaluation, Molecular Docking, and SAR Studies of Novel 2-(2,4-Dihydroxyphenyl)-1H- Benzimidazole Analogues

et al. 2019

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In the present study, new 4-(1H-benzimidazol-2-yl)-benzene-1,3-diols, modified in both rings, have been synthesized and their efficacies as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors have been determined.The modified Ellman's spectrophotometric method was applied for the biological evaluation. The compounds showed strong (IC 50 80-90 nM) AChE and moderate (IC 50 5-0.2 µM) BuChE inhibition in vitro. Some compounds were effective toward AChE/BuChE, exhibiting high selectivity ratios versus BuChE, while the other compounds were active against both enzymes. The structure-activity relationships were discussed. The compounds inhibited also in vitro self-induced Aβ(1-42) aggregation and exhibited antioxidant properties. The docking simulations showed that the benzimidazoles under consideration interact mainly with the catalytic site of AChE and mimic the binding mode of tacrine.

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Section: Introductionmentioning

confidence: 99%

Biological Evaluation, Molecular Docking, and SAR Studies of Novel 2-(2,4-Dihydroxyphenyl)-1H- Benzimidazole Analogues

et al. 2019

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“…This lead molecule should be considered for further pharmacological development. Among the various known thiadiazol derivatives [187][188][189][190] the (1,3,4-thiadiazol-2-yl) benzene-1,3-diol derivative 121 ( Figure 23) was a mixed type and potent AChE inhibitor (IC 50 = 53 nM) with 950 fold selectivity index over BChE (IC 50 = 50200 nM) in electric eel [188]. Figure 24) showed 60% AChE inhibition, which was stronger than donepezil (40% inhibition)in pharmacological studies at 2.6351 mM in adult male albino Wister rats [191].…”

Section: Novel Heterocyclic Moleculesmentioning

confidence: 99%

The Structural Hybrids of Acetylcholinesterase Inhibitors in the Treatment of Alzheimer’s Disease: A Review

Saxena¹

2019

AND

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Alzheimer's Disease (AD) is characterized by the loss of memory and learning ability in elderly patients affecting large population worldwide. The enzyme Acetylcholinesterase (AChE), (E.C.3.1.1.7) plays a major role in the hydrolysis of the released neurotransmitter acetylcholine. Most of the clinically used drugs to treat AD are Acetylcholinesterase Inhibitors (AChEIs). These drugs can provide symptomatic benefits only and suffer with loss of therapeutic potential with time. Therefore, there is an urgent need of novel cholinesterase inhibitors with wider therapeutic window for the treatment of AD. The strategies targeting the AChE enzyme along with other target(s) like Butyrylcholinesterase (BChE), amyloid-β (Aβ), β-secretase-1 (BACE), metals (Cu 2+ , Zn 2+ , or Fe 2+), antioxidant properties and free radical scavenging capacity have been mainly focused in the last five years. A number of hybrid molecules incorporating sub-structures with the desired well-established pharmacological profile into a single scaffold have been investigated. The main sub structures used in developing these molecules are derived from diverse chemical classes such as acridine, quinoline, carbamates, huperzine and other heterocyclic analogs. It has been followed by optimization of activity through structural modifications of the prototype molecules for developing the Structure Activity Relationship (SAR). This has led to the development of novel molecules with desired AChE inhibitory activity along with other desirable pharmacological properties. This review summarizes the current therapeutic strategies for the development of these AChEI in the last seven years.

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“…They display a broad spectrum of biological activities including antimicrobial, 1 anticancer, 2,3 antioxidant, 4 antidepressant, 5 anticonvulsant, 6,7 and antihypertensive activity, 8 as well as acetylcholinesterase inhibitors for the treatment of Alzheimer disease. 9,10 In addition, thiourea derivatives are key synthons for the synthesis of biologically active heterocycles with a broad spectrum of medicinal applications. 11 In particular, the most significant thiourea derivatives demonstrated antiviral, 12 anti-HIV, 13 antifungal, 14 and anticancer activities.…”

Section: Introductionmentioning

confidence: 99%

Synthetic access to some new benzothiazole-based 1,3,4-thiadiazole and 1,3-thiazole derivatives

Dawood¹,

Ragab²,

Ali³

2016

Turk J Chem

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1-(Benzothiazol-2-yl)-3-phenylthiourea 2 was prepared and treated with hydrazonoyl chlorides 3a-e to yield the corresponding 5-(benzothiazol-2-ylimino)-1,3,4-thiadiazole derivatives 6a-e, respectively. Reaction of the thiourea derivative 2 with ethyl 2-chloro-3-oxobutanoate 9 afforded the corresponding 2-(benzothiazol-2-ylimino)thiazole-5-carboxylate derivative 11. The newly synthesized heterocyclic derivatives were confirmed from their elemental and spectral analyses.

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Synthesis and anticholinesterase activities of novel 1,3,4-thiadiazole based compounds

Cited by 30 publications

References 20 publications

Biological Evaluation, Molecular Docking, and SAR Studies of Novel 2-(2,4-Dihydroxyphenyl)-1H- Benzimidazole Analogues

Biological Evaluation, Molecular Docking, and SAR Studies of Novel 2-(2,4-Dihydroxyphenyl)-1H- Benzimidazole Analogues

The Structural Hybrids of Acetylcholinesterase Inhibitors in the Treatment of Alzheimer’s Disease: A Review

Synthetic access to some new benzothiazole-based 1,3,4-thiadiazole and 1,3-thiazole derivatives

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