Recognizing novel drugs against Keap1 in Alzheimer’s disease using machine learning grounded computational studies

Mukerjee, Nobendu; Al-Khafaji, Khattab; Maitra, Swastika; Wadi, Jaafar Suhail; Sachdeva, Punya; Ghosh, Arabinda; Buchade, Rahul Subhash; Chaudhari, Somdatta Yashwant; Jadhav, Shailaja B.; Das, Padmashree; Hasan, Mohammad Mehedi; Rahman, Md. Habibur; Albadrani, Ghadeer M.; Altyar, Ahmed E.; Kamel, Mohamed S.; Algahtani, Mohammad; Shinan, Khlood; Theyab, Abdulrahman; Abdel‐Daim, Mohamed M.; Ashraf, Ghulam Md; Rahman, Md. Mominur; Sharma, Rohit

doi:10.3389/fnmol.2022.1036552

Cited by 16 publications

(10 citation statements)

References 28 publications

(39 reference statements)

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“…Our analysis revealed that the primary contributors to ΔGbind, which stabilizes the simulated complex, are ΔGbindCoulomb, ΔGbindvdW, and ΔGbindLipo. In contrast, ΔGbindCovalent and ΔGbindSolvGB contribute to the instability of the complex ( Mukerjee, 2022 ). These findings underscore the high binding free energy observed for the Neuropilins-PI3K complex, indicating its efficient binding capacity and ability to form a stable complex with Neuropilins.…”

Section: Resultsmentioning

confidence: 99%

In silico and in vitro study of bioactive compounds of Nigella sativa for targeting neuropilins in breast cancer

Zafar,

Safder,

Imran Afridi

et al. 2023

Front. Chem.

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Introduction: Breast cancer poses a significant global challenge, prompting researchers to explore novel approaches for potential treatments.Material and Methods: For in vitro study we used thin layer chromatography (TAC) for phytochemical screening, total antioxidant capacity (TLC) assay for antioxidant capacity, and hemolytic activity test for toxicity of Neuropilins (NRPs). We performed bioinformatic analyses to predict protein structures, molecular docking, pharmacophore modeling, and virtual screening to reveal interactions with oncogenes. We conducted 200 ns Molecular Dynamics (MD) simulations and MMGBSA calculations to assess the complex dynamics and stability.Results: We identified phytochemical constituents in Nigella sativa leaves, including tannins, saponins, steroids, and cardiac glycosides, while phlobatannins and terpenoids were absent. The leaves contained 9.4% ± 0.04% alkaloids and 1.9% ± 0.05% saponins. Methanol extract exhibited the highest yield and antioxidant capacity, with Total Flavonoid Content at 127.51 ± 0.76 mg/100 g and Total Phenolic Content at 134.39 ± 0.589 mg GAE/100 g. Hemolysis testing showed varying degrees of hemolysis for different extracts. In-silico analysis indicated stable Neuropilin complexes with key signaling pathways relevant for anti-cancer therapy. Molecular docking scores at different possesses (0, C-50, C −80, C-120,C −150, C −200 ns) revealed strong hydrogen bonding in the complexes and showed −12.9, −11.6, and −11.2 binding Affinities (kcal/mol) to support their stability. Our MD simulations analysis at 200ns confirmed the stability of Neuropilin complexes with the signaling pathways protein PI3K. The calculated binding free energies using MMGBSA provided valuable quantitative information on ligand potency on different time steps. These findings highlight the potential health benefits of N. sativa leaves and their possible role in anti-cancer treatments targeting angiogenesis.Conclusion:Nigella sativa leaves have shown significant medical potential due to their bioactive compounds, which exhibit strong properties in supporting organogenic processes related to cancer. Furthermore, studies have highlighted the promising role of neuropilins in anticancer treatment, demonstrating stable interactions and potential as targeted therapy specifically for breast cancer.

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Section: Resultsmentioning

confidence: 99%

In silico and in vitro study of bioactive compounds of Nigella sativa for targeting neuropilins in breast cancer

Zafar,

Safder,

Imran Afridi

et al. 2023

Front. Chem.

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“…Therefore, it has been confirmed in numerous studies that depression as a neurodegenerative disorder resulting in atrophy of the brain regions 21 . Neurodegenerative disorders develop due to loss of neurons, resulting in a decline in cognitive functioning of the brain 22–28 . Several studies have identified the hippocampus as the key brain region linked to depression, and hippocampal plasticity occurs in patients with depression 29 .…”

Section: Overview On Depressionmentioning

confidence: 96%

Ketamine as a therapeutic agent in major depressive disorder and posttraumatic stress disorder: Potential medicinal and deleterious effects

Sachdeva

Sachdeva²,

Ghosh

et al. 2023

Ibrain

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Major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) are the most common causes of emotional distress that impair an individual's quality of life. MDD is a chronic mental illness that affects 300 million people across the world. Clinical manifestations of MDD include fatigue, loss of interest in routine tasks, psychomotor agitation, impaired ability to focus, suicidal ideation, hypersomnolence, altered psychosocial functioning, and appetite loss. Individuals with depression also demonstrate a reduced behavioral response while experiencing pleasure, a symptom known as anhedonia. Like MDD, PTSD is a prevalent and debilitating psychiatric disorder resulting from a traumatic incident such as sexual assault, war, severe accident, or natural disaster. Symptoms such as recalling event phases, hypervigilance, irritability, and anhedonia are common in PTSD. Both MDD and PTSD pose enormous socioeconomic burdens across the globe. The search for effective treatment with minimal side effects is still ongoing. Ketamine is known for its anesthetic and analgesic properties. Psychedelic and psychotropic effects of ketamine have been found on the nervous system, which highlights its toxicity. In this article, the effectiveness of ketamine as a potential therapeutic for PTSD and MDD along with its mechanisms of action, clinical trials, and possible side effects have been discussed.

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“…Neurodegenerative disorders are conditions in which the central nervous system cells stop functioning or die [ 51 , 52 , 53 ]. The majority of neurodegenerative diseases are incurable and often worsen with time [ 54 , 55 ].…”

Section: Depression As a Neurodegenerative Disordermentioning

confidence: 99%

Plausible Role of Stem Cell Types for Treating and Understanding the Pathophysiology of Depression

Sachdeva¹,

Ghosh

et al. 2023

Pharmaceutics

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Major Depressive Disorder (MDD), colloquially known as depression, is a debilitating condition affecting an estimated 3.8% of the population globally, of which 5.0% are adults and 5.7% are above the age of 60. MDD is differentiated from common mood changes and short-lived emotional responses due to subtle alterations in gray and white matter, including the frontal lobe, hippocampus, temporal lobe, thalamus, striatum, and amygdala. It can be detrimental to a person’s overall health if it occurs with moderate or severe intensity. It can render a person suffering terribly to perform inadequately in their personal, professional, and social lives. Depression, at its peak, can lead to suicidal thoughts and ideation. Antidepressants manage clinical depression and function by modulating the serotonin, norepinephrine, and dopamine neurotransmitter levels in the brain. Patients with MDD positively respond to antidepressants, but 10–30% do not recuperate or have a partial response accompanied by poor life quality, suicidal ideation, self-injurious behavior, and an increased relapse rate. Recent research shows that mesenchymal stem cells and iPSCs may be responsible for lowering depression by producing more neurons with increased cortical connections. This narrative review discusses the plausible functions of various stem cell types in treating and understanding depression pathophysiology.

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Recognizing novel drugs against Keap1 in Alzheimer’s disease using machine learning grounded computational studies

Cited by 16 publications

References 28 publications

In silico and in vitro study of bioactive compounds of Nigella sativa for targeting neuropilins in breast cancer

In silico and in vitro study of bioactive compounds of Nigella sativa for targeting neuropilins in breast cancer

Ketamine as a therapeutic agent in major depressive disorder and posttraumatic stress disorder: Potential medicinal and deleterious effects

Plausible Role of Stem Cell Types for Treating and Understanding the Pathophysiology of Depression

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