Identification of FDA compounds to inhibit RAGEs through docking, MD-simulation, MMPBSA and DFT analysis DOI Creative Commons
Akash Pratap Singh, Shaban Ahmad, Khalid Raza

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 15, 2023

Abstract Receptor for advanced glycation end products (RAGEs) is a multifunctional cell surface protein present in vascular cells, monocytes/macrophages, B- and T-lymphocytes, retina Muller kidney podocytes, mesangial glial neurons, some cancer cells. The variety of types expresses RAGE, AGEs ligand recognized by these receptor produce signaling cascade mechanisms. Accumulation recognisase RAGEs play important roles diabetes, chronic inflammatory disorders, neurological illnesses, cancer, as well T-lymphocyte proliferation. Therefore, block the activity through FDA inhibitors are unmet need. In this studies, we targeted RAGE screening libraries docking analysis. Docking studies identifed best four compounds Zytiga (ZINC000003797541), Paliperidone (ZINC000004214700), Targretin (ZINC000001539579), Irinotecan (ZINC000001612996) Carboxymethyllysine (Control) were medications examined; their respective ΔG values -11.2, -11.1 -5.0 kcal/mol respectively. Furthermore, 100 ns run was performed found RMSD value Paliperidone(1.2±0.3 nm) (1.3± 0.2 quite stable. Next, simulation experiment supported MMPBSA analysis molecule high negative energy (-13.49 kcal/mol). silico investigation suggested that involved stable interactions which maintained throughout MD with RAGEs, virtually. results advocated could potentially inhibit be used clinical management various diseases.

Language: Английский

Drug target screening for Rheumatoid Arthritis by Curcuma caesia through computational approach. DOI Creative Commons

Ankita Pati,

Mahendra Gaur, Abhinav Jauhari Ankit Sahu

et al.

Current Plant Biology, Journal Year: 2025, Volume and Issue: unknown, P. 100468 - 100468

Published: March 1, 2025

Language: Английский

Citations

1
Plants as Biofactories for Therapeutic Proteins and Antiviral Compounds to Combat COVID-19 DOI Creative Commons

Corbin England,

Jonathan TrejoMartinez,

Paula PerezSanchez

et al.

Life, Journal Year: 2023, Volume and Issue: 13(3), P. 617 - 617

Published: Feb. 23, 2023

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome 2 (SARS-CoV-2) had a profound impact on the world’s health and economy. Although end pandemic may come in 2023, it is generally believed that virus will not be completely eradicated. Most likely, become an endemicity. rapid development vaccines different types (mRNA, subunit protein, inactivated virus, etc.) some other antiviral drugs (Remdesivir, Olumiant, Paxlovid, has provided effectiveness reducing COVID-19’s worldwide. However, circulating SARS-CoV-2 been constantly mutating with emergence multiple variants, which makes control COVID-19 difficult. There still pressing need for developing more effective to fight against disease. Plants have promising production platform both bioactive chemical compounds (small molecules) recombinant therapeutics (big molecules). naturally produce diverse range as secondary metabolites, such alkaloids, terpenoids/terpenes polyphenols, are rich source countless compounds. can also genetically engineered valuable therapeutics. This molecular farming plants unprecedented opportunity vaccines, antibodies, biologics diseases because its potential advantages, low cost, safety, high volume. review summarizes latest advancements plant-derived used combat discusses prospects challenges plant-based agents.

Language: Английский

Citations

15
Investigating the Inhibitory Effects of Paliperidone on RAGEs: Docking, DFT, MD Simulations, MMPBSA, MTT, Apoptosis, and Immunoblotting Studies DOI Open Access
Akash Pratap Singh, Shaban Ahmad,

Anamika Roy

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1060 - 1060

Published: Jan. 26, 2025

Chronic diseases such as diabetes and cancer are the leading causes of mortality worldwide. Receptors for Advanced Glycation End products (RAGEs) ubiquitous factors that catalyse (AGEs), proteins, lipids become glycated from sugar ingestion. RAGEs cell surface receptor proteins play a broad role in mediating effects AGEs on cells, contributing to modifying biological macromolecules like lipids, which can cause Reactive Oxygen Species (ROS) generation, inflammation, cancer. We targeted RAGE inhibition analysis screening United States Food Drug Administration (FDA) libraries through molecular docking studies identified four most suitable FDA compounds: Zytiga, Paliperidone, Targretin, Irinotecan. compared them with control substrate, Carboxymethyllysine, showed good binding interaction hydrogen bonding, hydrophobic interactions, π-stacking at active site residues target protein. Following 100 ns simulation run, docked complex revealed Root Mean Square Deviation (RMSD) values two drugs, Irinotecan (1.3 ± 0.2 nm) Paliperidone (1.2 0.3 nm), were relatively stable. Subsequently, Molecular Mechanics Poisson–Boltzmann Surface Area (MMPBSA) determined molecule had high negative energy −13.49 kcal/mol, Absorption, Distribution, Metabolism, Excretion (ADME) properties use mentioned cases. extended this many vitro studies, including an immunoblotting assay, High Mobility Group Box 1 (HMGB1) higher expression, while lower expressions. Furthermore, proliferation assay Apoptosis (Annexin-V/PI staining) results was effective anti-glycation anti-apoptotic drug—however, more extensive vivo needed before its use.

Language: Английский

Citations

0
Integrating genome-wide CRISPR screens and in silico drug profiling for targeted antidote development DOI
Bei Wang,

Yu Xu,

Arabella Wan

et al.

Nature Protocols, Journal Year: 2024, Volume and Issue: 19(9), P. 2739 - 2770

Published: May 30, 2024

Language: Английский

Citations

3
GC–MS analysis, molecular docking, and apoptotic-based cytotoxic effect of Caladium lindenii Madison extracts toward the HeLa cervical cancer cell line DOI Creative Commons

Aasia Kalsoom,

Awais Altaf,

Muhammad Sarwar

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Aug. 8, 2024

Utilizing medicinal plants and other natural resources to prevent different types of human cancers is the prime focus attention. Cervical cancer in women ranks as fourth most common type malignancy. The current study used gas chromatography-mass spectrometry (GC-MS) identify active phytochemical constituents from Caladium lindenii leaf extracts using ethanol (ECL) n-hexane (HCL) solvents. Plant were tested for potential cytotoxic effects on HeLa HEK-293 T cells MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) crystal violet assays. SYBR Green-based real-time PCR was performed assess mRNA expression profile apoptosis biomarkers (BCL-2 TP53). molecular interaction compounds with targeted proteins (TP53, BCL2, EGFR, HER2) determined docking. GC-MS analysis revealed a total 93 both extracts. ECL extract significantly reduced proliferation cervical cells, an IC

Language: Английский

Citations

2
Gene expression and anticancer evaluation of Kigelia africana (Lam.) Benth. Extracts using MDA-MB-231 and MCF-7 cell lines DOI Creative Commons

Aasia Kalsoom,

Awais Altaf,

Huma Sattar

et al.

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(6), P. e0303134 - e0303134

Published: June 5, 2024

In recent years, a cancer research trend has shifted towards identifying novel therapeutic compounds from natural assets for the management of cancer. this study, we aimed to assess cytotoxic activity Kigelia Africana (KA) extracts on breast (MDA-MB-231 and MCF-7) noncancerous kidney cells (HEK-293T) develop an efficient anticancer medication. We used gas chromatography mass spectrometry (GC-MS analyze constituents EKA HKA meanwhile crystal violet MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assays were examine possible effects plant our cell lines along with non-cancerous control. The quantitative real-time PCR (RT-PCR) was run samples evaluate differential expression proliferative markers (BCL-2 TP53). These phytochemicals have been reported binding affinity some other growth factors receptors as well which evaluated by in-silico molecular docking against Bcl2, EGFR, HER2, TP53. Our Morphological observation showed significant difference in morphology proliferation potential decreased under effect treatment compared control samples. ethanol extract exhibited marked antiproliferative MDA-MB-231 MCF-7 IC 50 = 20 32 μg/mL, respectively. Quantitative RT-PCR gene investigation revealed that concentration ethanolic regulated levels mRNA apoptotic genes. With target active site amino acids discovered investigation, TP53/Propanoic acid, 3-(2, 3, 6-trimethyl-1, 4-dioxaspiro [4.4] non-7-yl)-, methyl ester (-7.1 kcal/mol) is best-docked ligand. use folk remedies justifies its high vitro anti-cancer capabilities. This work highlights role inhibition proliferation. Based all these findings, it can be concluded promising anti-proliferative cancerous but more study required future further narrow down ingredients total crude specific targets cells.

Language: Английский

Citations

1
The Potential Role of Medicinal Plants, Traditional Herbal Medicines, and Formulations to Overcome SARS-CoV-2 Induced Health Crisis DOI
Mihir Halder, Rahul Bose, Sumita Jha

et al.

Sustainable development and biodiversity, Journal Year: 2023, Volume and Issue: unknown, P. 465 - 524

Published: Jan. 1, 2023

Language: Английский

Citations

1
Identification of FDA compounds to inhibit RAGEs through docking, MD-simulation, MMPBSA and DFT analysis DOI Creative Commons
Akash Pratap Singh, Shaban Ahmad, Khalid Raza

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 15, 2023

Abstract Receptor for advanced glycation end products (RAGEs) is a multifunctional cell surface protein present in vascular cells, monocytes/macrophages, B- and T-lymphocytes, retina Muller kidney podocytes, mesangial glial neurons, some cancer cells. The variety of types expresses RAGE, AGEs ligand recognized by these receptor produce signaling cascade mechanisms. Accumulation recognisase RAGEs play important roles diabetes, chronic inflammatory disorders, neurological illnesses, cancer, as well T-lymphocyte proliferation. Therefore, block the activity through FDA inhibitors are unmet need. In this studies, we targeted RAGE screening libraries docking analysis. Docking studies identifed best four compounds Zytiga (ZINC000003797541), Paliperidone (ZINC000004214700), Targretin (ZINC000001539579), Irinotecan (ZINC000001612996) Carboxymethyllysine (Control) were medications examined; their respective ΔG values -11.2, -11.1 -5.0 kcal/mol respectively. Furthermore, 100 ns run was performed found RMSD value Paliperidone(1.2±0.3 nm) (1.3± 0.2 quite stable. Next, simulation experiment supported MMPBSA analysis molecule high negative energy (-13.49 kcal/mol). silico investigation suggested that involved stable interactions which maintained throughout MD with RAGEs, virtually. results advocated could potentially inhibit be used clinical management various diseases.

Language: Английский

Citations

0