Probing 4-(diethylamino)-salicylaldehyde-based thiosemicarbazones as multi-target directed ligands against cholinesterases, carbonic anhydrases and α-glycosidase enzymes

Hashmi, Sadaf; Khan, Samra; Shafiq, Zahid; Taslimi, Parham; Ishaq, Muhammad; Sadeghian, Nastaran; Karaman, Halide Sedef; Akhtar, Naeem; Islam, Muhammad; Asari, Asnuzilawati; Mohamad, Habsah; Gülçın, İlhami

doi:10.1016/j.bioorg.2020.104554

Cited by 66 publications

(42 citation statements)

References 67 publications

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“…In parallel, thiosemicarbazones also display a wide plethora of biological properties ranging from anticancer, anti-bacterial, anti-tumor, anti-protozoal, anti-fungal, anti-leishmanial, and antiviral activities [29][30][31][32][33][34]. Thiosemicarbazone derivatives have also been employed as NDRG1 up-regulators, cathepsin inhibitors, and cholinesterase inhibitors for the treatment of Alzheimer's disease [35][36][37][38]. Figure 1 represents illustrative examples of commercial drugs for AD therapy and importance of quinoline as well as thiosemicarbazone in medicinal/pharmaceutical chemistry.…”

Section: Introductionmentioning

confidence: 99%

Hybrid Quinoline-Thiosemicarbazone Therapeutics as a New Treatment Opportunity for Alzheimer’s Disease‒Synthesis, In Vitro Cholinesterase Inhibitory Potential and Computational Modeling Analysis

et al. 2021

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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia worldwide. The limited pharmacological approaches based on cholinesterase inhibitors only provide symptomatic relief to AD patients. Moreover, the adverse side effects such as nausea, vomiting, loss of appetite, muscle cramps, and headaches associated with these drugs and numerous clinical trial failures present substantial limitations on the use of medications and call for a detailed insight of disease heterogeneity and development of preventive and multifactorial therapeutic strategies on urgent basis. In this context, we herein report a series of quinoline-thiosemicarbazone hybrid therapeutics as selective and potent inhibitors of cholinesterases. A facile multistep synthetic approach was utilized to generate target structures bearing multiple sites for chemical modifications and establishing drug-receptor interactions. The structures of all the synthesized compounds were fully established using readily available spectroscopic techniques (FTIR, 1H- and 13C-NMR). In vitro inhibitory results revealed compound 5b as a promising and lead inhibitor with an IC50 value of 0.12 ± 0.02 μM, a 5-fold higher potency than standard drug (galantamine; IC50 = 0.62 ± 0.01 μM). The synergistic effect of electron-rich (methoxy) group and ethylmorpholine moiety in quinoline-thiosemicarbazone conjugates contributes significantly in improving the inhibition level. Molecular docking analysis revealed various vital interactions of potent compounds with amino acid residues and reinforced the in vitro results. Kinetics experiments revealed the competitive mode of inhibition while ADME properties favored the translation of identified inhibitors into safe and promising drug candidates for pre-clinical testing. Collectively, inhibitory activity data and results from key physicochemical properties merit further research to ensure the design and development of safe and high-quality drug candidates for Alzheimer’s disease.

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Section: Introductionmentioning

confidence: 99%

Hybrid Quinoline-Thiosemicarbazone Therapeutics as a New Treatment Opportunity for Alzheimer’s Disease‒Synthesis, In Vitro Cholinesterase Inhibitory Potential and Computational Modeling Analysis

et al. 2021

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“…The results show that EEFO as a crude extract exhibited efficient α-glycosidase and α-amylase inhibition effect than that of acarbose, which had IC50 of 10.00 μM for α-amylase, 22.80 μM for a-glucosidase. The results clearly showed that EEFO had more effective inhibition than that of acarbose, which was a starch blocker [77].…”

Section: Resultsmentioning

confidence: 92%

Anticholinergic, Antidiabetic and Antioxidant Activities of Ferula orientalis L. Determination of Its Polyphenol Contents by LC-HRMS

Kızıltaş¹,

Gören²,

Bingöl³

et al. 2021

Rec.Nat.Prod.

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To evaluate the antioxidant activity of evaporated ethanolic extract of Ferula orientalis L. (EEFO) and lyophilized water extract of Ferula orientalis L. (WEFO) several in vitro antioxidant methods such as ABTS•+ scavenging activity, DPPH· scavenging activity, Fe3+reduction method, cupric ions (Cu2+) reduction capacity, and metal ion (Fe2+)-binding activities using ferrozine reagent were separately performed. Also, BHT, α-tocopherol and ascorbic acid were used as the standard antioxidant molecules. Moreover, some phenolic compounds that are responsible for antioxidant abilities of EEFO and WEFO were determined by LC-HRMS. EEFO and WEFO demonstrated effective antioxidant abilities when compared with the standards. EEFO demonstrated IC50 values of 1.946 µg/mL against acetylcholinesterase (AChE), 0.815 µg/mL against α-glycosidase, and 0.675 µg/mL against α-amylase.

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“…The results show that EESB as a crude extract exhibited efficient both digestive inhibition effects than acarbose, which had IC 50 of 10.00 mmol/L for α-amylase, 22.80 mmol/L for α-glycosidase. The results showed that EESB had more effective inhibition than that of acarbose as a starch blocker [81].…”

Section: Resultsmentioning

confidence: 98%

Antidiabetic, anticholinergic and antioxidant activities of aerial parts of shaggy bindweed (Convulvulus betonicifolia Miller subsp.) – profiling of phenolic compounds by LC-HRMS

Bingöl

Kızıltaş

Gören

et al. 2021

Heliyon

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In order to evaluate the antioxidant activity of evaporated ethanolic extract (EESB) and lyophilized water extract (WESB) of Shaggy bindweed (Convulvulus betonicifolia Mill. Subs), some putative antioxidant methods such as DPPH⋅ scavenging activity, ABTS þ scavenging effect, ferric ions (Fe 3þ ) reduction method, cupric ions (Cu 2þ ) reducing capacity, and ferrous ions (Fe 2þ ) binding activities were separately performed. Also, ascorbic acid, α-tocopherol and BHT were used as the standard compounds. Additionally, some phenolic compounds that responsible for antioxidant abilities of EESB and WESB were screened by liquid chromatography-high resolution mass spectrometry (LC-HRMS). At the same concentration, EESB and WESB demonstrated effective antioxidant abilities when compared to standards. In addition, EESB demonstrated IC 50 values of 1.946 μg/mL against acetylcholinesterase (AChE), 0.815 μg/mL against α-glycosidase and 0.675 μg/mL against α-amylase enzymes.

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Probing 4-(diethylamino)-salicylaldehyde-based thiosemicarbazones as multi-target directed ligands against cholinesterases, carbonic anhydrases and α-glycosidase enzymes

Cited by 66 publications

References 67 publications

Hybrid Quinoline-Thiosemicarbazone Therapeutics as a New Treatment Opportunity for Alzheimer’s Disease‒Synthesis, In Vitro Cholinesterase Inhibitory Potential and Computational Modeling Analysis

Hybrid Quinoline-Thiosemicarbazone Therapeutics as a New Treatment Opportunity for Alzheimer’s Disease‒Synthesis, In Vitro Cholinesterase Inhibitory Potential and Computational Modeling Analysis

Anticholinergic, Antidiabetic and Antioxidant Activities of Ferula orientalis L. Determination of Its Polyphenol Contents by LC-HRMS

Antidiabetic, anticholinergic and antioxidant activities of aerial parts of shaggy bindweed (Convulvulus betonicifolia Miller subsp.) – profiling of phenolic compounds by LC-HRMS

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