Synthesis, in-vitro α-glucosidase inhibition, antioxidant, in-vivo antidiabetic and molecular docking studies of pyrrolidine-2,5-dione and thiazolidine-2,4-dione derivatives

Hussain, Fida; Najam, Zeeshan; Jan, Muhammad; Ahmad, Sajjad; Ahmad, Ashfaq; Rashid, Umer; Ullah, Farhat; Ayaz, Muhammad; Sadiq, Abdul

doi:10.1016/j.bioorg.2019.103128

Cited by 83 publications

(50 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…25 Succinimides or 2.5-dioxopyrrolidines, a well-known class of drugs, possess a variety of biological potentials. 26,27 The basic structure can be derivatized by various aryl and/or alkyl groups on nitrogen or carbon positions. 28,29 Formerly, succinimides had been synthesized through various methods.…”

Section: Introductionmentioning

confidence: 99%

Comparative Cholinesterase, α-Glucosidase Inhibitory, Antioxidant, Molecular Docking, and Kinetic Studies on Potent Succinimide Derivatives

Ahmad

Ullah

Sadiq

et al. 2020

DDDT

Self Cite

View full text Add to dashboard Cite

Introduction: The current study was designed to synthesize derivatives of succinimide and compare their biological potency in anticholinesterase, alpha-glucosidase inhibition, and antioxidant assays. Methods: In this research, two succinimide derivatives including (S)-1-(2,5-dioxo-1-phenylpyrrolidin-3-yl) cyclohexanecarbaldehyde (Compound 1) and (R)-2-((S)-2,5-dioxo-1-phenylpyrrolidin-3-yl)-2-phenylpropanal (Compound 2) were synthesized using Michael addition. Both the compounds, ie, 1 and 2 were evaluated for in-vitro acetylcholinesterase (AChE), butyrylctcholinesterase (BChE), antioxidant, and α-glucosidase inhibitory potentials. Furthermore, molecular docking was performed using Molecular Operating Environment (MOE) to explore the binding mode of both the compounds against different enzymes. Lineweaver-Burk plots of enzyme inhibitions representing the reciprocal of initial enzyme velocity versus the reciprocal of substrate concentration in the presence of synthesized compounds and standard drugs were constructed using Michaelis-Menten kinetics. Results: In AChE inhibitory assay, compounds 1 and 2 exhibited IC 50 of 343.45 and 422.98 µM, respectively, against AChE enzyme. Similarly, both the compounds showed IC 50 of 276.86 and 357.91 µM, respectively, against BChE enzyme. Compounds 1 and 2 displayed IC 50 of 157.71 and 471.79 µM against α-glucosidase enzyme, respectively. In a similar pattern, compound 1 exhibited to be more potent as compared to compound 2 in all the three antioxidant assays. Compound 1 exhibited IC 50 values of 297.98, 332.94, and 825.92 µM against DPPH, ABTS, and H 2 O 2 free radicals, respectively. Molecular docking showed a triple fold in the AChE and BChE activity for compound 1 compared with compound 2. The compound 1 revealed good interaction against both the AChE and BChE enzymes which revealed the high potency of this compound compared to compound 2. Conclusion: Both succinimide derivatives exhibited considerable inhibitory activities against cholinesterases and α-glucosidase enzymes. Of these two, compound 1 revealed to be more potent against all the in-vitro targets which was supported by molecular docking with the lowest binding energies. Moreover, compound 1 also proved to have antiradical properties.

show abstract

Section: Introductionmentioning

confidence: 99%

Comparative Cholinesterase, α-Glucosidase Inhibitory, Antioxidant, Molecular Docking, and Kinetic Studies on Potent Succinimide Derivatives

Ahmad

Ullah

Sadiq

et al. 2020

DDDT

Self Cite

View full text Add to dashboard Cite

show abstract

“…The ABTS anti-radicals assay was used following our previously reported procedures 35,36. In brief, various solutions including K 2 S 2 O 4 and ABTS (7 mM) were prepared and combined.…”

Section: Methodsmentioning

confidence: 99%

Pharmacological Evaluation of Aldehydic-Pyrrolidinedione Against HCT-116, MDA-MB231, NIH/3T3, MCF-7 Cancer Cell Lines, Antioxidant and Enzyme Inhibition Studies

Ahmad

Ullah

Sadiq

et al. 2019

DDDT

Self Cite

View full text Add to dashboard Cite

PurposeThe current work was designed to synthesize a bioactive derivative of succinimide and evaluate it for anti-Alzheimer, anticancer and anti-diabetic potentials.MethodsThe compound was synthesized by Michael addition of butyraldehyde with N-phenylmaleimide. The synthesized compound was screened for biological potentials including anti-cholinesterase, in-vitro anti-diabetic, antioxidant and anthelmintic potentials. The anti-cholinesterase potential was evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), anti-diabetic potential against α-glucosidase, antioxidant potential against ABTS, DPPH and H2O2 and anthelmintic potential against Perethima posthuma and Ascaridia galli respectively.ResultsThe compound demonstrated significant AChE and BChE inhibition i.e., 71.34±1.92 and 73.42 ±1.92 at the concentration of 1000 µg/mL respectively. Other dilutions exhibited concentration-dependent inhibitory activity against both enzymes. In the MTT assay, the newly synthesized compound was found active against all of the cell lines viz, HCT-116, MDA-MB231, NIH/3T3 and MCF-7 and the highest cytotoxicity potential was observed against the colon cancer cell line (HCT-116) with an IC50 value of 78 µg/mL exhibiting its highest potential. Moreover, the compound exhibited prominent α-glucosidase inhibitory potentials (79.86±2.54% at 1000 µg/mL) with IC50 value of 156.23 µg/mL. Further, our test compound exhibited considerable scavenging activity against DPPH, ABTS and H2O2 free radicals with percent inhibitions of 75.84±1.58, 72.85±1.17 and 54.82±1.82 and IC50 values of 84.36, 139.74 and 752.21 µg/mL respectively. Our test sample exhibited significant anthelmintic potentials. It demonstrated significant paralysis and death of the test worms in an unbelievably short time in comparison with albendazole.ConclusionGoing into the detail of all observations, it may be deduced that the newly synthesized succinimide derivative could be an important drug candidate against neurodegenerative disorders like Alzheimer’s disease, cancer, diabetes mellitus and worms. Further detailed studies in animal models are required for in-vivo analysis of the compound.

show abstract

“…The emission spectra of the synthesized ligand in chloroform and of complexes in acetonitrile were obtained by using a fluorescence spectrophotometer. The emission spectra were checked by keeping the excitation value of the synthesized compounds at 325 nm [40,[67][68][69][70][71][72]. The fluorescence spectra have been observed at 335 nm for ligands (L 1 -L 9 ) and 520 nm for complexes royalsocietypublishing.org/journal/rsos R. Soc.…”

Section: Photo-luminescence Studiesmentioning

confidence: 99%

Terpyridine-metal complexes: effects of different substituents on their physico-chemical properties and density functional theory studies

Mughal¹,

Mirzaei

Sadiq³

et al. 2020

R. Soc. open sci.

View full text Add to dashboard Cite

A series of different substituted terpyridine (tpy)-based ligands have been synthesized by Kröhnke method. Their binding behaviour was evaluated by complexing them with Co(II), Fe(II) and Zn(II) ions, which resulted in interesting coordination compounds with formulae, [Zn(tpy) 2 ]PF 6 , [Co(tpy) 2 ](PF 6 ) 2 , [Fe(tpy) 2 ](PF 6 ) 2 and interesting spectroscopic properties. Their absorption and emission behaviours in dilute solutions were investigated in order to explain structure–property associations and demonstrate the impact of different aryl substituents on the terpyridine scaffold as well as the role of the metal on the complexes. Photo-luminescence analysis of the complexes in acetonitrile solution revealed a transition from hypsochromic to bathochromic shift. All the compounds displayed remarkable photo-luminescent properties and various maximum emission peaks owing to the different nature of the functional groups. Furthermore, the anti-microbial potential of ligands and complexes was evaluated with docking analyses carried out to investigate the binding affinity of terpyridine-based ligands along with corresponding proteins (shikimate dehydrogenase and penicillin-binding protein) binding sites. To obtain further insight into molecular orbital distributions and spectroscopic properties, density functional theory calculations were performed for representative complexes. The photophysical activity and interactions between chromophore structure and properties were both investigated experimentally as well as theoretically.

show abstract

Synthesis, in-vitro α-glucosidase inhibition, antioxidant, in-vivo antidiabetic and molecular docking studies of pyrrolidine-2,5-dione and thiazolidine-2,4-dione derivatives

Cited by 83 publications

References 36 publications

<p>Comparative Cholinesterase, α-Glucosidase Inhibitory, Antioxidant, Molecular Docking, and Kinetic Studies on Potent Succinimide Derivatives</p>

<p>Comparative Cholinesterase, α-Glucosidase Inhibitory, Antioxidant, Molecular Docking, and Kinetic Studies on Potent Succinimide Derivatives</p>

<p>Pharmacological Evaluation of Aldehydic-Pyrrolidinedione Against HCT-116, MDA-MB231, NIH/3T3, MCF-7 Cancer Cell Lines, Antioxidant and Enzyme Inhibition Studies</p>

Terpyridine-metal complexes: effects of different substituents on their physico-chemical properties and density functional theory studies

Contact Info

Product

Resources

About