In Silico Approaches to Developing Novel Glycogen Synthase Kinase 3β (GSK-3β) DOI Creative Commons
Shuchi Goyal, Manjinder Singh, Divya Thirumal

и другие.

Biomedicines, Год журнала: 2023, Номер 11(10), С. 2784 - 2784

Опубликована: Окт. 13, 2023

Alzheimer's disease (AD) is caused by plaque agglomeration and entanglement in several areas of the neural cells, which leads to apoptosis. The main etiology AD senile dementia, linked amyloid-beta (Aβ) deregulation tau perivascular pathogeny. Hyperphosphorylated has a propensity for microtubules, elevate instability tau-protein congregates, leading accumulation neurofibrillary tangles (NFTs). Tau hyperphosphorylation susceptible GSK-3, led an emerging hypothesis regarding pathogenesis AD. Accordingly, attempts have been made conduct investigations achieve further advancements on new analogues capable inhibiting GSK-3 protein, are currently clinical trials. In this analysis, we evaluated certain inhibitor variants utilising scaffolding framework devised techniques with pharmacological characteristics, accompanied computational screenings (pharmacokinetics docking). structure-based designed interacted effectively active amino acids GSK-3β target protein. silico pharmacokinetic studies revealed their drug-like properties. best interactions binding scores will be considered future completely demonstrate potential relevance as viable inhibitors.

Язык: Английский

Practical Three-Component Regioselective Synthesis of Drug-Like 3-Aryl(or heteroaryl)-5,6-dihydrobenzo[h]cinnolines as Potential Non-Covalent Multi-Targeting Inhibitors To Combat Neurodegenerative Diseases DOI
Hossein Mousavi, Mehdi Rimaz, Behzad Zeynizadeh

и другие.

ACS Chemical Neuroscience, Год журнала: 2024, Номер 15(9), С. 1828 - 1881

Опубликована: Апрель 22, 2024

Neurodegenerative diseases (NDs) are one of the prominent health challenges facing contemporary society, and many efforts have been made to overcome (or) control it. In this research paper, we described a practical one-pot two-step three-component reaction between 3,4-dihydronaphthalen-1(2H)-one (1), aryl(or heteroaryl)glyoxal monohydrates (2a–h), hydrazine monohydrate (NH2NH2•H2O) for regioselective preparation some 3-aryl(or heteroaryl)-5,6-dihydrobenzo[h]cinnoline derivatives (3a–h). After synthesis characterization mentioned cinnolines (3a–h), in silico multi-targeting inhibitory properties these heterocyclic scaffolds investigated upon various Homo sapiens-type enzymes, including hMAO-A, hMAO-B, hAChE, hBChE, hBACE-1, hBACE-2, hNQO-1, hNQO-2, hnNOS, hiNOS, hPARP-1, hPARP-2, hLRRK-2(G2019S), hGSK-3β, hp38α MAPK, hJNK-3, hOGA, hNMDA receptor, hnSMase-2, hIDO-1, hCOMT, hLIMK-1, hLIMK-2, hRIPK-1, hUCH-L1, hPARK-7, hDHODH, which confirmed their functions roles neurodegenerative (NDs), based on molecular docking studies, obtained results were compared with wide range approved drugs well-known (with IC50, EC50, etc.) compounds. addition, ADMET prediction analysis was performed examine prospective drug synthesized compounds The from studies ADMET-related data demonstrated that series heteroaryl)-5,6-dihydrobenzo[h]cinnolines especially hit ones, can really be turned into potent core new treatment and/or due having reactionable locations, they able further organic reactions (such as cross-coupling reactions), expansion (for example, using other types monohydrates) makes avenue designing novel efficient purpose.

Язык: Английский

Процитировано

8
Computational Studies to Understand the Neuroprotective Mechanism of Action Basil Compounds DOI Creative Commons
Varinder Singh, Somdutt Mujwar, Manjinder Singh

и другие.

Molecules, Год журнала: 2023, Номер 28(20), С. 7005 - 7005

Опубликована: Окт. 10, 2023

Neurodegenerative diseases, such as Alzheimer's and Parkinson's, pose a significant global health challenge, emphasizing the need for novel neuroprotective agents. Basil (Ocimum spp.) has been recognized its therapeutic potential, numerous studies have reported effects. In this manuscript, we present computational protocol to extricate underlying mechanism of action basil compounds in Molecular docking-based investigation chemical interactions between selected bioactive from key targets, including AChE, GSK3β, γ-secretase, sirtuin2. Our results demonstrate that compound myricerone caffeoyl ester possesses high affinity -10.01 -8.85 kcal/mol against GSK3β respectively, indicating their potential modulating various neurobiological processes. Additionally, molecular dynamics simulations were performed explore protein-ligand complexes' stability analyze bound compounds' dynamic behavior. This comprehensive enlightens putative mechanistic basis effects compounds, providing rationale use neurodegenerative disorders after further experimental validation.

Язык: Английский

Процитировано

7
BACE1 inhibitors: A promising therapeutic approach for the management of Alzheimer’s disease DOI Creative Commons
Richa Arya, Smita Jain, Sarvesh Paliwal

и другие.

Asian Pacific Journal of Tropical Biomedicine, Год журнала: 2024, Номер 14(9), С. 369 - 381

Опубликована: Сен. 1, 2024

Alzheimer’s disease is a neurological disorder marked by the accumulation of amyloid beta (Aβ) aggregates, resulting from mutations in precursor protein. The enzyme β-secretase, also known as β-site protein cleaving 1 (BACE1), plays crucial role generating Aβ peptides. With no targeted therapy available for disease, inhibiting BACE1 aspartic protease has emerged primary treatment target. Since 1999, compounds demonstrating potential binding to receptor have advanced human trials. Structural optimization synthetically derived compounds, coupled with computational approaches, offered valuable insights developing highly selective leads drug-like properties. This review highlights pivotal studies on design and development inhibitors anti-Alzheimer’s agents. It summarizes methods employed facilitating drug discovery provides an update their clinical status, indicating future directions novel inhibitors. promising results Elenbecestat (E-2609) catalyze effective, future.

Язык: Английский

Процитировано

2
Exploring the molecular mechanisms underlying neuroprotective effect of ellagic acid in okadaic acid-induced Alzheimer’s phenotype DOI
Tourandokht Baluchnejadmojarad, Mehrdad Roghani

Metabolic Brain Disease, Год журнала: 2024, Номер 39(7), С. 1417 - 1432

Опубликована: Авг. 12, 2024

Язык: Английский

Процитировано

0
In Silico Approaches to Developing Novel Glycogen Synthase Kinase 3β (GSK-3β) DOI Creative Commons
Shuchi Goyal, Manjinder Singh, Divya Thirumal

и другие.

Biomedicines, Год журнала: 2023, Номер 11(10), С. 2784 - 2784

Опубликована: Окт. 13, 2023

Alzheimer's disease (AD) is caused by plaque agglomeration and entanglement in several areas of the neural cells, which leads to apoptosis. The main etiology AD senile dementia, linked amyloid-beta (Aβ) deregulation tau perivascular pathogeny. Hyperphosphorylated has a propensity for microtubules, elevate instability tau-protein congregates, leading accumulation neurofibrillary tangles (NFTs). Tau hyperphosphorylation susceptible GSK-3, led an emerging hypothesis regarding pathogenesis AD. Accordingly, attempts have been made conduct investigations achieve further advancements on new analogues capable inhibiting GSK-3 protein, are currently clinical trials. In this analysis, we evaluated certain inhibitor variants utilising scaffolding framework devised techniques with pharmacological characteristics, accompanied computational screenings (pharmacokinetics docking). structure-based designed interacted effectively active amino acids GSK-3β target protein. silico pharmacokinetic studies revealed their drug-like properties. best interactions binding scores will be considered future completely demonstrate potential relevance as viable inhibitors.

Язык: Английский

Процитировано

0