Design, Synthesis, and biological evaluation of pyrazolo-benzothiazole derivatives as a potential therapeutic agent for the treatment of Alzheimer’s disease

Kumar, Harvindra Singh; Goyal, Anju; Kumar, Navneet; Garg, Pooja

doi:10.1007/s00044-022-02953-4

Cited by 4 publications

(4 citation statements)

References 46 publications

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“…AD is a chronic age‐related brain disease characterized by the gradual cognitive decline, memory loss, excessive neuronal loss, and memory functions (Kumar, Goyal et al, 2022; Shi et al, 2021; Ying He et al, 2023). It is coupled with excessive loss of the neurotransmitter ACh causing dementia symptoms and leading to permanent memory loss over the period of time.…”

Section: Conclusion and Perspectivementioning

confidence: 99%

Berberine derivatives as inhibitors of acetylcholinesterase: A systematic review

Singh,

Kumar

2023

Chem Biol Drug Des

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Alzheimer's disease (AD) is a chronic age‐related neurodegenerative brain disorder characterized by the impairment of memory accompanied by worsening of thinking ability of an individual. The exact pathophysiology of AD is not fully understood. However low level of the neurotransmitter named acetylcholine (ACh), aggregation of Aβ peptide into toxic Aβ plaque, hyperphosphorylation of tau, bio‐metal imbalance, and oxidative stress are the main hallmarks of this disease. Due to the complex pathophysiology of AD, no specific treatment is available in the market, and treatment is only limited to the symptomatic relief. So, there is an urgent need for the development of new drug candidate, which can have disease‐modifying effect and improve learning and memory in AD patient. Therefore, berberine‐based multifunction compounds with potential cholinesterase inhibitory properties were reviewed in this article. Structure–activity relationship (SAR) and biological activity provide highlights on the new derivatives used for the management of AD.

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Section: Conclusion and Perspectivementioning

confidence: 99%

Berberine derivatives as inhibitors of acetylcholinesterase: A systematic review

Singh,

Kumar

2023

Chem Biol Drug Des

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“…Molecular docking studies also indicate that this compound fits fully into the active sites of h AChE. [ 46 ] Compounds D shows inhibitory activity against both enzymes MAO‐A and MAO‐B, with IC 50 values of 17.00 ± 0.89 and 2.95 ± 0.09 μM, respectively. [ 47 ] Therefore, synthesis of derivatives based on benzo[ d ]thiazole heterocycles is an active area of research.…”

Section: Introductionmentioning

confidence: 99%

Sulfonyl thioureas with a benzo[d]thiazole ring as dual acetylcholinesterase/butyrylcholinesterase and human monoamine oxidase A and B inhibitors: An in vitro and in silico study

Dinh Thanh,

Son Hai,

Ngoc Toan

et al. 2024

Archiv der Pharmazie

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A series of sulfonyl thioureas 6a–q containing a benzo[d]thiazole ring with an ester functional group was synthesized from corresponding substituted 2‐aminobenzo[d]thiazoles 3a–q and p‐toluenesulfonyl isothiocyanate. They had remarkable inhibitory activity against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), monoamine oxidase (MAO)‐A, and MAO‐B. Among thioureas, several compounds had notable activity in the order of 6k > 6 h > 6c (AChE), 6j > 6g > 6k (BChE), 6k > 6g > 6f (MAO‐A), and 6i > 6k > 6h (MAO‐B). Compound 6k was an inhibitor of interest due to its potent or good activity against all studied enzymes, with IC50 values of 0.027 ± 0.008 μM (AChE), 0.043 ± 0.004 μM (BChE), 0.353 ± 0.01 μM (MAO‐A), and 0.716 ± 0.02 μM (MAO‐B). This inhibitory capacity was comparable to that of the reference drugs for each enzyme. Kinetic studies of two compounds with potential activity, 6k (against AChE) and 6j (against BChE), had shown that both 6k and 6j followed competitive‐type enzyme inhibition, with Ki constants of 24.49 and 12.16 nM, respectively. Induced fit docking studies for enzymes 4EY7, 7BO4, 2BXR, and 2BYB showed active interactions between sulfonyl thioureas of benzo[d]thiazoles and the residues in the active pocket with ligands 6k, 6i, and 6j, respectively. The stability of the ligand–protein complexes while each ligand entered the active site of each enzyme (4EY7, 7BO4, 2BXR, or 2BYB) was confirmed by molecular dynamics simulations.

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“…In a recent study, Kumar et al synthesized pyrazolo-benzothiazole analogs and analyzed their acetylcholine esterase and antioxidant activities. [17] Additionally, a recent investigation of the benzothiazole-based derivatives aimed to evaluate the anticancer properties against Michigan Cancer Foundation-7 (MCF-7) and hepatoblastoma cell line (HepG-2). [18] The cancer studies of BTA analogs have reported naphthalimide derivatives with unique benzothiazole and thiazole moieties, as well as benzofuran or benzothiazole bis-thiazole hybrid derivatives.…”

Section: Introductionmentioning

confidence: 99%

“…In a recent study, Kumar et al. synthesized pyrazolo‐benzothiazole analogs and analyzed their acetylcholine esterase and antioxidant activities [17] . Additionally, a recent investigation of the benzothiazole‐based derivatives aimed to evaluate the anticancer properties against Michigan Cancer Foundation‐7 (MCF‐7) and hepatoblastoma cell line (HepG‐2) [18] .…”

Section: Introductionmentioning

confidence: 99%

In Vitro and In Silico Evaluation of Amylase, Tyrosinase, and Pancreatic Lipase Inhibitions of Novel Benzothiazole‐Sulfonate Derivatives

Korkmaz,

Bursal,

Kurtay

2023

ChemistrySelect

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This paper provides a comprehensive account of the synthesis and assessment of newly developed aryl sulfonate derivatives based on benzothiazole as enzyme inhibitors, specifically focusing on their ability to target tyrosinase, amylase, and pancreatic lipase. The assessments were performed utilizing experimental (in vitro) and computational (in silico) methodologies. For this aim, nine different aryl sulfonate derivatives were synthesized. The synthesized compounds were subjected to structural characterizations by utilizing Nuclear Magnetic Resonance (1H NMR, 13C NMR) and High‐Resolution Mass Spectrometry (HRMS) studies, which provided confirmation of their structural properties. The inhibitory efficiency of the compounds was determined by measuring their 50 % inhibitory concentration (IC50) values and comparing them with the standard inhibitory compounds. According to the in vitro amylase activity, benzo[d]thiazol‐2‐yl 4‐methylbenzenesulfonate showed the best inhibition with the lowest IC50 value (43.31±4.3 μM) which was calculated to be at a close level to the IC50 value of standard acarbose (38.50±3.8 μM). Also, benzo[d]thiazol‐2‐yl 4‐bromobenzenesulfonate (22.73±4.15 μM) and benzo[d]thiazol‐2‐yl 4‐chlorobenzenesulfonate (25.28±1.95 μM) were calculated to have the lowest IC50 values and the most effective inhibition capacities against pancreatic lipase. Benzo[d]thiazol‐2‐yl 4‐fluorobenzenesulfonate and benzo[d]thiazol‐2‐yl 4‐methylbenzenesulfonate significantly exhibited superior tyrosinase inhibition compared to other derivatives and conventional kojic acid. In silico molecular docking affirmed that benzo[d]thiazol‐2‐yl naphthalene‐2‐sulfonate presented the highest binding affinities to the studied enzymes, with values of −7.8 kcal/mol for tyrosinase, −10.7 kcal/mol for pancreatic lipase, and −9.4 kcal/mol for α‐amylase. The pharmacokinetic characteristics and drug‐likeness of the synthesized sulfonate derivatives were also evaluated using absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction. Density Functional Theory (DFT) calculations were employed at the DFT/B3LYP/6‐311 g(d,p) level of theory to investigate the electronic characteristics of the compounds, therefore facilitating the comprehension of the reported enzyme inhibitory actions. In summary, our research highlights the potential of benzothiazole aryl sulfonate derivatives as effective enzyme inhibitors that hold promise for therapeutic applications.

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Design, Synthesis, and biological evaluation of pyrazolo-benzothiazole derivatives as a potential therapeutic agent for the treatment of Alzheimer’s disease

Cited by 4 publications

References 46 publications

Berberine derivatives as inhibitors of acetylcholinesterase: A systematic review

Berberine derivatives as inhibitors of acetylcholinesterase: A systematic review

Sulfonyl thioureas with a benzo[d]thiazole ring as dual acetylcholinesterase/butyrylcholinesterase and human monoamine oxidase A and B inhibitors: An in vitro and in silico study

In Vitro and In Silico Evaluation of Amylase, Tyrosinase, and Pancreatic Lipase Inhibitions of Novel Benzothiazole‐Sulfonate Derivatives

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