Cholinesterases inhibition and molecular modeling studies of piperidyl-thienyl and 2-pyrazoline derivatives of chalcones

Shah, Muhammad Shakil; Khan, Shafi Ullah; Ejaz, Syeda Abida; Afridi, Saifullah; Rizvi, Syed Umar Farooq; Najam‐ul‐Haq, Muhammad; Iqbal, Jamshed

doi:10.1016/j.bbrc.2016.11.082

Cited by 35 publications

(20 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These compounds were used in the development of drug research and agricultural products . In the previous studies, it was indicated that these compounds have significant pharmacological and biological activities . Many pyrazoline compounds are reported to possess a broad spectrum of biological activities such as antimicrobial, antidepressant, neuroprotective, anticonvulsant, anti‐inflammatory, analgesic, antitubercular, local anesthetic, hypoglycemic, hypotensive, insecticide, herbicide, and molluscicidal .…”

Section: Introductionmentioning

confidence: 99%

Synthesis, characterization, molecular docking and biological activities of novel pyrazoline derivatives

Türkan

Çetin

Taslimi

et al. 2019

Archiv der Pharmazie

View full text Add to dashboard Cite

In this study, synthesis of ethyl 2-((4-bromophenyl)diazenyl)-3-oxo-phenylpropanoate 1 was carried out and a series of new 3H-pyrazol-3-ones (P1-7) were synthesized from 1 as well as various hydrazines. The obtained yields of the synthesized compounds were moderate (40-70%) and these compounds were confirmed by spectral data. These novel pyrazoline derivatives were effective inhibitor compounds of the human carbonic anhydrase I and II isozymes (hCAs I and II) and of the acetylcholinesterase (AChE) enzyme, with K i values in the range of 17.4-40.7 nM for hCA I, 16.1-55.2 nM for hCA II, and 48.2-84.1 nM for AChE. In silico studies were performed on the compounds inhibiting hCA I, hCA II, and AChE receptors. On the basis of the findings, the inhibition profile of the new pyrazoline compounds at the receptors was determined.

show abstract

Section: Introductionmentioning

confidence: 99%

Synthesis, characterization, molecular docking and biological activities of novel pyrazoline derivatives

Türkan

Çetin

Taslimi

et al. 2019

Archiv der Pharmazie

View full text Add to dashboard Cite

show abstract

“…For the last few years, chalcones, belonging to flavonoid derivatives, have attracted great interest due to their diverse bioactivities, encompassing antimalarial [ 13 , 14 ], antimicrobial [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ], antioxidant [ 28 ], antitumor [ 29 , 30 , 31 ], anti-inflammatory [ 32 , 33 , 34 ], analgesic [ 34 , 35 , 36 ], to antiulcer [ 37 , 38 ]. Recent studies have also indicated the abilities of chalcones in inhibiting enzymes, including alpha-glucosidase [ 39 , 40 ], lipoxygenase [ 33 , 41 ], mammalian alpha-amylase [ 42 , 43 ], xanthine oxidase [ 44 ], monoamine oxidase (MAO) [ 45 , 46 , 47 ], especially acetylcholinesterase [ 48 , 49 , 50 , 51 , 52 ] and beta-secretase (BACE-1) [ 53 , 54 ]. Therefore, the research of bioactivities of chalcone derivatives on the function of human brain, especially AChE and BACE-1 provides great promise in the discovery of new therapeutic agents for a range of neurological diseases including AD.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, In Silico and In Vitro Evaluation for Acetylcholinesterase and BACE-1 Inhibitory Activity of Some N-Substituted-4-Phenothiazine-Chalcones

Thai

Nguyen

et al. 2020

Molecules

View full text Add to dashboard Cite

Acetylcholinesterase (AChE) and beta-secretase (BACE-1) are two attractive targets in the discovery of novel substances that could control multiple aspects of Alzheimer’s disease (AD). Chalcones are the flavonoid derivatives with diverse bioactivities, including AChE and BACE-1 inhibition. In this study, a series of N-substituted-4-phenothiazine-chalcones was synthesized and tested for AChE and BACE-1 inhibitory activities. In silico models, including two-dimensional quantitative structure–activity relationship (2D-QSAR) for AChE and BACE-1 inhibitors, and molecular docking investigation, were developed to elucidate the experimental process. The results indicated that 13 chalcone derivatives were synthesized with relatively high yields (39–81%). The bioactivities of these substances were examined with pIC50 3.73–5.96 (AChE) and 5.20–6.81 (BACE-1). Eleven of synthesized chalcones had completely new structures. Two substances AC4 and AC12 exhibited the highest biological activities on both AChE and BACE-1. These substances could be employed for further researches. In addition to this, the present study results suggested that, by using a combination of two types of predictive models, 2D-QSAR and molecular docking, it was possible to estimate the biological activities of the prepared compounds with relatively high accuracy.

show abstract

“…Pyrazolines, as one of the most important heterocyclic compounds in medicinal chemistry, have various biological activities such as anti‐Alzheimer, anti‐Parkinson, and antidepressant . They show their effects by inhibiting or activating several enzymes such as cholinesterases, monoamine oxidases, and carbonic anhydrases.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, molecular modeling, and biological evaluation of 4‐[5‐aryl‐3‐(thiophen‐2‐yl)‐4,5‐dihydro‐1H‐pyrazol‐1‐yl] benzenesulfonamides toward acetylcholinesterase, carbonic anhydrase I and II enzymes

et al. 2017

View full text Add to dashboard Cite

In this study, 4-[5-aryl-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl] benzenesulfonamides were synthesized, and inhibition effects on AChE, hCA I, and hCA II were evaluated. K values of the compounds toward hCA I were in the range of 24.2 ± 4.6-49.8 ± 12.8 nm, while they were in the range of 37.3 ± 9.0-65.3 ± 16.7 nm toward hCA II. K values of the acetazolamide were 282.1 ± 19.7 nm and 103.60 ± 27.6 nm toward both isoenzymes, respectively. The compounds inhibited AChE with K in the range of 22.7 ± 10.3-109.1 ± 27.0 nm, whereas the tacrine had K value of 66.5 ± 13.8 nm. Electronic structure calculations at M06-L/6-31 + G(d,p)//AM1 level and molecular docking studies were also performed to enlighten inhibition mechanism and to support experimental findings. Results obtained from calculations of molecular properties showed that the compounds obey drug-likeness properties. The experimental and computational findings obtained in this study might be useful in the design of novel inhibitors against hCA I, hCA II, and AChE.

show abstract

Cholinesterases inhibition and molecular modeling studies of piperidyl-thienyl and 2-pyrazoline derivatives of chalcones

Cited by 35 publications

References 28 publications

Synthesis, characterization, molecular docking and biological activities of novel pyrazoline derivatives

Synthesis, characterization, molecular docking and biological activities of novel pyrazoline derivatives

Synthesis, In Silico and In Vitro Evaluation for Acetylcholinesterase and BACE-1 Inhibitory Activity of Some N-Substituted-4-Phenothiazine-Chalcones

Synthesis, molecular modeling, and biological evaluation of 4‐[5‐aryl‐3‐(thiophen‐2‐yl)‐4,5‐dihydro‐1H‐pyrazol‐1‐yl] benzenesulfonamides toward acetylcholinesterase, carbonic anhydrase I and II enzymes

Contact Info

Product

Resources

About