Design, synthesis, extra-precision docking, and molecular dynamics simulation studies of pyrrolidin-2-one derivatives as potential acetylcholinesterase inhibitors

Gupta, Mohan L.; Kumar, Avinash; Prasun, Chakrawarti; Nair, Maya S.; Kini, Suvarna G.; Yadav, Divya; Nain, Sumitra

doi:10.1080/07391102.2022.2106515

Cited by 4 publications

(4 citation statements)

References 33 publications

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“…Scopolamine hydrobromide and Donepezil hydrochloride were brought from Merck (Merck KGaA, Darmstadt, Germany).Trichloroacetic acid, acetylthiocholine iodide, 5,5′-dithiobisnitrobenzoic acid (DTNB), hydroxylamine hydrochloride, and ferric chloride, were brought from Sigma-Aldrich (St. Louis, MO, USA). Synthetic pyridine-2-one derivatives 28 , 28a – e previously synthesized by our group were used in the study [ 11 ]. All other reagents and chemicals utilized in the investigation were of analytical grade.…”

Section: Methodsmentioning

confidence: 99%

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The memory ameliorating effects of novel N-benzyl pyridine-2-one derivatives on scopolamine-induced cognitive deficits in mice

Pant,

Gupta,

Anthwal

et al. 2024

Lab Anim Res

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Background Alzheimer's disease (AD), the most common form of progressive dementia in the elderly, is a chronic neurological disorder that decreases cognitive ability. Although the underlying cause of AD is yet unknown, oxidative stress and brain acetylcholine shortage are the key pathogenic causes. Results The current study shows that these derivatives have the potential to improve memory in mice by inhibiting scopolamine-induced acetylcholinesterase activity, oxidative and nitrosative stress, and improving locomotor activity and muscle grip strength in the rota rod test. When compared to the illness control, the memory-enhancing potential of novel N-benzyl pyridine-2-one derivatives was highly significant (P < 0.0001). Conclusions The observed memory ameliorating effect of novel N-benzyl pyridine-2-one makes them as a a good choice for treatment of individuals with cognitive impairment. Graphical abstract

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Section: Methodsmentioning

confidence: 99%

“…These derivatives were created earlier and assessed using the molecular docking method (Fig. 5 ) [ 11 ]. The molecular docking investigations against AChE enzymes yielded encouraging results.…”

Section: Introductionmentioning

confidence: 99%

The memory ameliorating effects of novel N-benzyl pyridine-2-one derivatives on scopolamine-induced cognitive deficits in mice

Pant,

Gupta,

Anthwal

et al. 2024

Lab Anim Res

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“…Unluckily, further chemical optimization of the lead compound pyrrolidine-2-one AChEI 80 did not lead to the identification of new benzoylpiperidine derivatives, but the best results were obtained by molecules belonging to other chemical classes [109].…”

Section: Ache Inhibitorsmentioning

confidence: 99%

The Benzoylpiperidine Fragment as a Privileged Structure in Medicinal Chemistry: A Comprehensive Review

Bononi,

Lonzi,

Tuccinardi

et al. 2024

Molecules

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The phenyl(piperidin-4-yl)methanone fragment (here referred to as the benzoylpiperidine fragment) is a privileged structure in the development of new drugs considering its presence in many bioactive small molecules with both therapeutic (such as anti-cancer, anti-psychotic, anti-thrombotic, anti-arrhythmic, anti-tubercular, anti-parasitic, anti-diabetic, and neuroprotective agents) and diagnostic properties. The benzoylpiperidine fragment is metabolically stable, and it is also considered a potential bioisostere of the piperazine ring, thus making it a feasible and reliable chemical frame to be exploited in drug design. Herein, we discuss the main therapeutic and diagnostic agents presenting the benzoylpiperidine motif in their structure, covering articles reported in the literature since 2000. A specific section is focused on the synthetic strategies adopted to obtain this versatile chemical portion.

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“…111 According to the recently reported studies, among the in silico results of FDA-approved drugs, the binding energies of donepezil were reported between -19.71 kcal/mol and -8.4 kcal/mol calculated by using various algorithms such as AutoDock Vina, Glide/ SP/XP, and MOE etc. [112][113][114][115][116][117][118][119][120][121][122][123][124][125][126][127][128] Furthermore, docking scores were given as -10.46 kcal/mol and -7.64 kcal/mol for donepezil and rivastigmine, respectively, by using Glide/ SP. 129 In our previously reported study, we calculated induced fit docking (IFD) and quantum polarized ligand docking (QPLD) scores as -12.20 kcal/mol and -9.54 kcal/mol for known inhibitor neostigmine, respectively, against AChE.…”

Section: In Silico Studiesmentioning

confidence: 99%

**Major Bioactive Prenylated Flavonoids from Humulus lupulus L., Their Applications in Human Diseases and Structure-Activity Relationships (SAR) – A Review**

Comert Onder,

Kalin,

Sahin

et al. 2023

Pharm Sci

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In recent years, the incidence of cancers, inflammatory diseases, Alzheimer’s disease, glucose metabolism disorder and diabetes has increased alarmingly which demands more research into the discovery of new drug candidates to treat these human diseases. Main phytochemicals from Humulus lupulus L. (hops) have been demonstrated to have positive impacts on human health, and prenylated flavonoids are one of the major groups of bioactive phytochemicals found in this plant. Thus, this review summarizes the role of major prenylated components in hops in human diseases including cancer, inflammation and viral infections. In silico studies of prenylated bioactive compounds against various drug targets such as histone deactylases (HDACs), sirtuins (SIRTs), and acetylcholinesterase (AChE), and the molecular molecular interactions between protein and ligand have also been included. Furthermore, the structure-activity relationships (SAR) studies on these compounds are highlighted. This review concludes that the prenylated phytochemicals from H. lupulus L., including xanthohumol (XN), isoxanthohumol (IXN), 8-prenylnaringenin (8-PN) and 6-prenylnaringenin (6-PN), have promising roles in human health and may contribute to new drug discovery and development.

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Design, synthesis, extra-precision docking, and molecular dynamics simulation studies of pyrrolidin-2-one derivatives as potential acetylcholinesterase inhibitors

Cited by 4 publications

References 33 publications

The memory ameliorating effects of novel N-benzyl pyridine-2-one derivatives on scopolamine-induced cognitive deficits in mice

The memory ameliorating effects of novel N-benzyl pyridine-2-one derivatives on scopolamine-induced cognitive deficits in mice

The Benzoylpiperidine Fragment as a Privileged Structure in Medicinal Chemistry: A Comprehensive Review

**Major Bioactive Prenylated Flavonoids from Humulus lupulus L., Their Applications in Human Diseases and Structure-Activity Relationships (SAR) – A Review**

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