Structure‐based pharmacophore modeling for precision inhibition of mutant ESR2 in breast cancer: A systematic computational approach

Cancer Medicine, Год журнала: 2024, Номер 13(15)

Опубликована: Авг. 1, 2024

Breast cancer, a leading cause of female mortality, is closely linked to mutations in estrogen receptor beta (ESR2), particularly the ligand-binding domain, which contributed altered signaling pathways and uncontrolled cell growth.

Язык: Английский

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Structure-guided identification of mitogen-activated protein kinase-1 inhibitors towards anticancer therapeutics

PLoS ONE, Год журнала: 2025, Номер 20(1), С. e0311954 - e0311954

Опубликована: Янв. 24, 2025

Mitogen-activated protein kinase 1 (MAPK1) is a serine/threonine that plays crucial role in the MAP signaling transduction pathway. This pathway various cellular processes, including cell proliferation, differentiation, adhesion, migration, and survival. Besides, many chemotherapeutic drugs targeting MAPK are used clinical practice, novel inhibitors of MAPK1 with improved specificity efficacy required. Hence, can be to control metastasis cancer therapeutics. In this study, we utilized structure-guided virtual screening approach screen library thousands natural compounds from ZINC database. The Lipinski rule five (RO5) was as criterion for primary selection compounds. screened were prioritized based on their binding affinity, docking scores, towards domain during molecular process. Subsequently, selected hits underwent rigorous included identification potential pan-assay interference (PAINS), ADMET evaluation, prediction pharmacological activities using PASS analysis. Afterwards, performed comprehensive interaction analysis explore prototypes molecules key residues within domain. Finally, extensive all-atom dynamics (MD) simulations time duration 200 nanoseconds. study pinpointed three database IDs ZINC0209285, ZINC02130647, ZINC02133691 MAPK1. highlights these could explored further preclinical investigations develop anticancer

Язык: Английский

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Determination of the Inhibitory Potential of Chalcones on Myeloperoxidase Enzyme Activity: In vitro and Molecular Docking Studies

Cell Biochemistry and Biophysics, Год журнала: 2025, Номер unknown

Опубликована: Март 13, 2025

Язык: Английский

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Identification of Potential DCAF1 Inhibitors Through Virtual Screening Based on Molecular Docking and Molecular Dynamics Simulations

ChemistrySelect, Год журнала: 2025, Номер 10(15)

Опубликована: Апрель 1, 2025

Abstract DCAF1 (DDB1‐ and CUL4‐associated factor 1) is an emerging anticancer target; however, few inhibitors have been identified so far. In this study, molecular docking of 24 known against structures revealed a significant correlation between Glide SP scores experimental Log10KD values ( R 2 = 0.723), thereby validating the reliability methodology. A virtual screening 1.4 million ChemDiv compounds protein structure using validated model led to identification 52 potential hit after applying several stringent filters, including docking, MM/GBSA scoring, REOS rules, cluster analysis. Among these hits, six with particularly favorable binding energies were subjected further in‐depth analysis 500 ns dynamics simulations. The results from simulations demonstrated that can bind high affinity, potentially impairing its biological function. Overall, computational workflow successfully novel inhibitor candidates, which are promising leads for optimization validation. This study represents advancement in search effective important yet underexplored target.

Язык: Английский

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Insilico discovery of novel Phosphodiesterase 4 (PDE4) inhibitors for the treatment of psoriasis: Insights from computer aided drug design approaches

PLoS ONE, Год журнала: 2024, Номер 19(11), С. e0305934 - e0305934

Опубликована: Ноя. 13, 2024

Psoriasis is chronic immune-mediated inflammatory disorder characterized by various comorbidities, erythematous plaques with silvery scale which can lead to psoriatic arthritis. The phosphodiesterase 4 (PDE4) protein a potential drug target control Psoriasis. In the current study, pharmacophore-based virtual screening of Diversity library ChemDiv database was first performed, and then screened hits were docked active site PDE4 choose best binding modes. Forty-six generated during prepared receptor SP docking module glide. affinities selected calculated molecular based on affinities, ten for bioactivity scores prediction ADMET analysis. Based profiling, four D356-2630, C700-2058, G842-0420 F403-0203 processed MD simulations stability outcomes showed that these compounds strong proteins better free energies. results our we proposed function as in biological assays vitro studies are required develop novel candidates.

Язык: Английский

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Exploring the conformational dynamics and key amino acids in the CD26-caveolin-1 interaction and potential therapeutic interventions

Medicine, Год журнала: 2024, Номер 103(22), С. e38367 - e38367

Опубликована: Май 31, 2024

This study aimed to decipher the interaction between CD26 and caveolin-1, key proteins involved in cell signaling linked various diseases. Using computational methods, we predicted their binding conformations assessed stability through 100 ns molecular dynamics (MD) simulations. We identified two distinct (con1 con4), with con1 exhibiting superior stability. In con1, specific amino acids CD26, namely GLU237, TYR241, TYR248, ARG147, were observed engage interactions F-J chain of Caveolin-1, establishing hydrogen bonds cation or π-π interactions. Meanwhile, con4, ARG253, LYS250, TYR248 interacted J Caveolin-1 via bonds, cation-π interactions, Virtual screening also revealed potential small-molecule modulators, including Crocin, Poliumoside, Canagliflozin, that could impact this interaction. Additionally, predictive analyses conducted on bioactivity, drug-likeness, ADMET properties these three compounds. These findings offer valuable insights into mechanism, paving way for new therapeutic strategies. However, further validation is required before clinical application. summary, provide a detailed understanding caveolin-1 interaction, identifying essential developing targeted therapies.

Язык: Английский

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Bioactive Compounds from Achyranthes Aspera L. Extract: A UHPLC Profile and In Silico Study for Mouth Cancer

ChemistrySelect, Год журнала: 2024, Номер 9(38)

Опубликована: Окт. 1, 2024

Abstract Mouth cancer is the most frequent of head and neck in both older younger people. Achyranthes aspera L. has been used ethnotraditional pharmacological applications since ancient times for a variety disorders. This study was formulated to examine bioactive phenolic flavonoid compounds from ethanolic extract their binding efficacy targeting growth factor receptors (GFRs) against mouth through silico molecular docking simulation studies. Phytochemicals were investigated UHPLC technique. A accomplished using software AutoDock 4.2, MD executed GROMACS software. Drug‐likeness, pharmacokinetics, toxicity profiles phytocompounds evaluated Molinspiration, Swiss ADME, OSIRIS Data Warrior tools, respectively. analysis detected phenolics flavonoids, viz., fisetin, rutin, fumaric acid, which satisfied Lipinski's rule five pharmacokinetic properties. In assessment, fisetin exhibited promising interactions with core targeted proteins VEGFR‐2 (B.E. = −8.30 kcal mol −1 ) FGFR‐2 −7.64 cancer. Moreover, dynamics data demonstrated stable proteins. interaction stability A. therapeutic might contribute potential management.

Язык: Английский

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Elucidating the monoamine oxidase B inhibitory effect of kaurene diterpenoids from Xylopia aethiopica: An in silico approach

PLoS ONE, Год журнала: 2024, Номер 19(11), С. e0308021 - e0308021

Опубликована: Ноя. 27, 2024

Parkinson disease is a neurogenerative common in adults and results different kinds of memory dysfuntions. This study evaluated the monoamine oxidase B (MAO-B) inhibitory potential kaurane diterpenoids previously isolated from Xylopia aethiopica through comprehensive computational approaches. Molecular docking molecular dynamics simulation were used to access binding mode interaction xylopic acid MAO-B enzyme. The ADMET properties phytochemical provide information on its druggability. revealed as inhibitor due good energy elicited stability throughout 100 ns period. ligand showed it promising drug candidate. recommend further vitro investigation towards development potent inhibitor.

Язык: Английский

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Galangin promotes apoptosis by upregulating the pro-apoptotic gene BAX in triple-negative breast cancer

Journal of the Egyptian National Cancer Institute, Год журнала: 2024, Номер 36(1)

Опубликована: Дек. 20, 2024

Abstract Background Triple-negative breast cancer (TNBC) is one of the most aggressive and formidable subtypes cancer, devoid targeted therapy frequently leading to unfavorable prognoses significant side effects. The demand for creative effective treatment options has prompted current study investigate potential natural chemicals as therapeutic agents. This intends examine efficacy Galangin, a naturally occurring flavonoid, in treating triple-negative cancer. Methods research utilizes dual methodology, combining silico network pharmacology with vitro experimental methods. proved crucial finding gene targets cellular signaling pathways influenced by Galangin To corroborate these computational predictions, variety studies were conducted, including MTT assay, wound scratch apoptosis reactive oxygen species mitochondrial membrane assessment, RT-PCR. Results Fifteen prevalent genes identified, demonstrating involvement proliferation, regulation, cell migration, MAPK cascade cycle regulation. predominant implicated ten principal MAPK1, MAPK8, MAPK14, IL6, which observed be linked pathway, perhaps serving critical channel through may facilitate oral In experiments demonstrated anti-proliferative effects, late-stage apoptosis, anti-migratory characteristics, antioxidant activity, upregulation pro-apoptotic BAX gene. Conclusion study’s results demonstrate that possesses considerable effects on TNBC cells, underscoring its viable drug. These findings development more precisely focused approaches TNBC, providing optimism enhanced outcomes patients suffering from this challenging disease.

Язык: Английский

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Investigating the chemo-preventive role of noscapine in lung carcinoma via therapeutic targeting of human aurora kinase B

Molecular and Cellular Biochemistry, Год журнала: 2024, Номер unknown

Опубликована: Июнь 3, 2024

Язык: Английский

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