Classes of Mormordicoside with potent and selective tumor cell growth inhibitory activity: prediction of Pyruvate kinase muscle isozyme 2 (PKM 2) and Anti-apoptotic Myeloid leukemia 1 (MCL1) inhibitor through machine learning. DOI Creative Commons
Tope Abraham Ibisanmi, ‪Jamiu Olaseni Aribisala, Peace Ifeoma Odjegba

et al.

Research Square (Research Square), Journal Year: 2022, Volume and Issue: unknown

Published: Sept. 22, 2022

Abstract Background The difficulty in treating cancer resides the ability to target abnormal proliferation while protecting normal proliferation, a feat that necessitates thorough comprehension of both and malignant mechanisms promote cell growth proliferation. Targeting death signaling pathways such as glycolytic mitochondrial apoptosis is hallmark many cancers aim which this research ready evaluate. Methods Atomistic molecular dynamics simulation top hits after docking ADMET profiling ligands were performed for main protease-hit complexes. Results Docking scores used against PKM2 ranges from – 9.36 12.1 kcal/mol, wherein, Mormordicoside-F2 had highest score (-12.1kcal/mol) performing better than FDA approved drug Benserazide(-7kcal/mol). Likewise, ranged between 8.51 12.05kcal/mol Anti-apoptotic Myeloid leukemia 1 (MCL-1), with Mormordicoside-F1 being ranked compound Venetoclax(-8.6 kcal/mol). RMSD plots obtained depicted stable trajectories consistent minor fluctuations implying protein (PKM2 MCL1) backbone underwent structural perturbations. In addition, several significant peaks increased (RMSF) also observed, indicating their interaction potential could adapt effectively binding pocket protein. SASA analysis results shows retained inside shallow pocket. phylogenetic tree implies likelihood reoccurring result Insilco profiling. Conclusion This unveils Mormordicoside F1 acceptable stability likewise F2 PKM2. These may offer more advantageous repurposing alternative.

Language: Английский

Herbal concoction Unveiled: A computational analysis of phytochemicals' pharmacokinetic and toxicological profiles using novel approach methodologies (NAMs) DOI Creative Commons

Mansi Rai,

Ajay Vikram Singh,

Namuna Paudel

et al.

Current Research in Toxicology, Journal Year: 2023, Volume and Issue: 5, P. 100118 - 100118

Published: Jan. 1, 2023

Herbal medications have an extensive history of use in treating various diseases, attributed to their perceived efficacy and safety. Traditional medicine practitioners contemporary healthcare providers shown particular interest herbal syrups, especially for respiratory illnesses associated with the SARS-CoV-2 virus. However, current understanding pharmacokinetic toxicological properties phytochemicals these mixtures is limited. This study presents a comprehensive computational analysis utilizing novel approach methodologies (NAMs) investigate profiles syrup, leveraging in-silico techniques prediction tools such as PubChem, SwissADME, Molsoft's database. Although molecular dynamics, docking, broader system-wide analyses were not considered, future studies hold potential further investigation areas. By combining drug-likeness simulation, researchers identify diverse suitable complex medication development examining pharmacokinetic-toxicological phytopharmaceutical syrup. The focuses on solutions infections, goal adding pool all-natural treatments ailments. research has revolutionize environmental alternative by models innovative analytical enhanced therapeutic benefits explore network-based systems biology approaches deeper interactions biological systems. Overall, our offers valuable insights into concoction. paves way advancements medicine. we acknowledge need address aforementioned topics that adequately covered this research.

Language: Английский

Citations

49
Antidiabetic Activity, Molecular Docking, and ADMET Properties of Compounds Isolated from Bioactive Ethyl Acetate Fraction of Ficus lutea Leaf Extract DOI Creative Commons
Oyinlola Oluwunmi Olaokun, Muhammad Sulaiman Zubair

Molecules, Journal Year: 2023, Volume and Issue: 28(23), P. 7717 - 7717

Published: Nov. 22, 2023

Diabetes contributes to the rising global death rate. Despite scientific advancements in understanding and managing diabetes, no single therapeutic agent has been identified effectively treat prevent its progression. Consequently, exploration for new antidiabetic therapeutics continues. This study aimed investigate bioactive ethyl acetate fraction of F. lutea at molecular level understand interactions ligand-protein binding. To do this, underwent column chromatography fractionation yield five compounds: lupeol, stigmasterol, α-amyrin acetate, epicatechin, epiafzelechin. These compounds were evaluated vitro through α-glucosidase inhibition glucose utilization assays C2C12 muscle H-4-11-E liver cells using standard methods. In silico analysis was conducted docking ADMET studies. Epicatechin exhibited most potent (IC50 = 5.72 ± 2.7 µg/mL), while epiafzelechin stimulated superior (33.35 1.8%) (46.7 1.2%) a concentration 250 µg/mL. The binding energies isolated glycogen phosphorylase (1NOI) α-amylase (1OSE) stronger (<-8.1) than those positive controls. Overall, all tested characteristics indicative their potential as agents; however, toxicity profiling predicted epicatechin better alternatives. compounds, particularly epiafzelechin, showed promise agents. However, further comprehensive studies are necessary validate these findings.

Language: Английский

Citations

18
In silico Drug Repurposing of Anticancer Drug 5-FU and Analogues Against SARS-CoV-2 Main Protease: Molecular Docking, Molecular Dynamics Simulation, Pharmacokinetics and Chemical Reactivity Studies DOI Creative Commons
Aristote Matondo, Washington Dendera, Bienfait Kabuyaya Isamura

et al.

Advances and Applications in Bioinformatics and Chemistry, Journal Year: 2022, Volume and Issue: Volume 15, P. 59 - 77

Published: Aug. 1, 2022

Background: Since the last COVID-19 outbreak, several approaches have been given a try to quickly tackle this global calamity. One of well-established strategies is drug repurposing, which consists in finding new therapeutic uses for approved drugs. Following same paradigm, we report present study, an investigation potential inhibitory activity 5-FU and nineteen its analogues against SARS-CoV-2 main protease (3CLpro). Material Methods: Molecular docking calculations were performed investigate binding affinity ligands within active site 3CLpro. The best candidates further considered molecular dynamics simulations 100 ns gain time-resolved understanding behavior guest-host complexes. Furthermore, profile druggability was assessed based on ADMET predictions. Finally, their chemical reactivity elucidated using different descriptors, namely electrostatic (MEP), Fukui functions frontier orbitals. Results Discussion: From performed, four (compounds 14, 15, 16 18) show promising results with respect target protease, 3CLpro, safety. These compounds are maintained inside 3CLpro thanks variety noncovalent interactions, especially hydrogen bonds, involving important amino acids such as GLU166, HIS163, GLY143, ASN142, HIS172, CYS145. suggest that well trapped protein over time gap ns, ligand 18 being most retained. Conclusion: In line findings reported herein, recommend in-vitro in-vivo investigations carried out shed light possible mechanism pharmacological action proposed ligands. Keywords: 5-fluorouracil, SARS-CoV-2, docking, simulation,

Language: Английский

Citations

17
Evaluation of antiviral potential of Cinchona officinalis derived compounds against COVID-19 and Human hepatitis B: An in silico Molecular Docking and Molecular Dynamics Simulation study DOI
Emmanuel Kitete Mulongo, Aristote Matondo, Koto-te-Nyiwa Ngbolua

et al.

Pharmacological Research - Natural Products, Journal Year: 2025, Volume and Issue: unknown, P. 100229 - 100229

Published: April 1, 2025

Language: Английский

Citations

0
In vitro evaluation of curcumin's antisickling activity and in silico analysis of curcuminoids and their ADMET properties DOI Creative Commons
Clément M. Mbadiko, Koto-te-Nyiwa Ngbolua, Gédéon Ngiala Bongo

et al.

Discover Chemistry., Journal Year: 2025, Volume and Issue: 2(1)

Published: May 11, 2025

Language: Английский

Citations

0
Exploring Moringa oleifera Phytochemicals as Potential Inhibitors for HIF- 1α/VEGF/GLUT1 pathway in Breast Cancer Using Molecular Docking, MD Simulations, and DFT Analysis DOI

Neha Masarkar,

Maynak Pal, Alakesh Bisai

et al.

Published: May 14, 2025

Abstract Breast cancer is among the most heterogeneous and aggressive diseases a foremost cause of death in women globally. Hypoxic activation HIF-1α breast cancers triggers transcription battery genes encoding proteins that facilitate tumor growth metastasis correlated with poor prognosis. Based on reported cytotoxic anti-cancer properties Moringa oleifera (Mo), this study explores inhibitory effect bioactive compounds AA BITC from oleifera target HIF-1α, VEGF, GLUT1 in silico. The X-ray crystallographic structures were sourced Protein Data Bank (PDB) docked 3D PubChem using AutoDock Vina, binding modes analyzed Discovery Studio. further drug-likeness, oral bioavailability, ADME, toxicity profiles SwissADME, ADMETSaR, ADMETlab 3.0 web server. Complexes subjected to molecular dynamic simulation (MDS) analysis Desmond Schrodinger v2019. Then, density functional theory (DFT) studies performed measure active compound’s reactivity, help Gaussian 09 software. Molecular docking results indicated ligands interact strongly receptors through Hydrogen bonds hydrophobic interactions. These showed favorable drug-like pharmacokinetic properties, possessed no substantial toxicity, fairly bioavailable. root-mean-square deviation (RMSD) graphs obtained simulations true bonding interactions, validated fluctuation (RMSF) which provided better understanding amino acids present responsible for motions fluctuations. Results suggested possess strong potential developing putative lead targeting are safe natural plant-based drugs against cancer.

Language: Английский

Citations

0
Anticancer, antioxidant, and antimicrobial properties of solvent extract of Lobophora variegata through in vitro and in silico studies with major phytoconstituents DOI

Nithya Palaniappan,

Balamuralikrishnan Balasubramanian, Arunkumar Malaisamy

et al.

Food Bioscience, Journal Year: 2022, Volume and Issue: 48, P. 101822 - 101822

Published: June 4, 2022

Language: Английский

Citations

15
Molecular docking and molecular dynamics simulation studies of the interaction of anti-oral cancer plant Curcuma longa derived-compounds with human epidermal growth factor receptor 2 DOI

Mfutu Mana Charly,

Koto-te-Nyiwa Ngbolua,

Jean-Paul Sekele Issouradi

et al.

Journal of Proteins and Proteomics, Journal Year: 2024, Volume and Issue: 15(3), P. 491 - 507

Published: July 16, 2024

Language: Английский

Citations

3
Cedrus deodara (Roxb. ex D.Don) G.Don bark fraction ameliorates metabolic, endocrine and ovarian dynamics in rats experiencing polycystic ovarian syndrome DOI
Akansha Bisht, Ritika Gururani, Smita Jain

et al.

Journal of Ethnopharmacology, Journal Year: 2023, Volume and Issue: 306, P. 116206 - 116206

Published: Jan. 21, 2023

Language: Английский

Citations

7
Synthesis, Molecular Docking, MD Simulation and Evaluation of Anticancer Activity of Novel 1,3,4-Oxadiazole derivatives against Ehrlich Ascites Carcinoma (EAC) Cell lines DOI

Shridhar Deshpande N,

S. R. NAIK,

D. Udayakumar

et al.

Journal of Computational Biophysics and Chemistry, Journal Year: 2024, Volume and Issue: 23(04), P. 519 - 539

Published: Feb. 25, 2024

In this study, a new series of 1,3,4-oxadiazole derivatives (3a– 3h) was synthesized, characterized using various analytical techniques (FT-IR, 1 H- and [Formula: see text]C-NMR, mass spectrometry), tested for their effectiveness against Ehrlich’s Ascites Carcinoma (EAC) cell lines in vitro. After 48 h exposure to these test compounds, the EAC cells exhibited dose-dependent reduction viability. Among 3b 3e demonstrated most potent anticancer effects, with IC[Formula: text] values 352.69 text]M 177.44 M, respectively. Consequently, compounds were chosen further investigation into mechanisms action on lines. The assessment included induction apoptosis analysis DNA damage, which evaluated fluorescence staining comet assay. These assessments revealed distinctive apoptotic characteristics such as nuclear fragmentation, cytoplasmic shrinkage damage. As result, hold promise potential agents. study also delved binding affinities through molecular docking analysis, findings showed that strong affinity receptor Transforming Growth Factor-Beta Receptor I (TGF-[Formula: text]RI) kinase (PDB ID: 1PY5), surpassing reference compound 5-fluorouracil. Additionally, calculations related Molecular Mechanics Generalized Born Surface Area (MM-GBSA) indicated favorable free energy. displayed acceptable ADMET properties. To validate stability bond between 1PY5 receptor, dynamics simulation lasting 100 ns carried out.

Language: Английский

Citations

2