Synergistic therapeutic strategies and engineered nanoparticles for anti-vascular endothelial growth factor therapy in cancer

Life Sciences, Journal Year: 2024, Volume and Issue: 341, P. 122499 - 122499

Published: Feb. 10, 2024

Language: Английский

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

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(1), P. e0311954 - e0311954

Published: Jan. 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

Language: Английский

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Targeting miRNA with flavonoids: unlocking novel pathways in cardiovascular disease management

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 6, 2025

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, with complex pathophysiological mechanisms such as oxidative stress, inflammation, apoptosis, and endothelial dysfunction driving progression. MicroRNAs (miRNAs), a class non-coding RNAs, have emerged key regulators gene expression involved in these processes, positioning them potential biomarkers therapeutic targets CVD management. Simultaneously, flavonoids, naturally occurring polyphenolic compounds found various plant-based foods, gained attention for their cardioprotective properties, including antioxidant, anti-inflammatory, anti-apoptotic effects. Recent studies suggest novel intersection between flavonoids miRNAs, where may modulate specific miRNAs implicated pathogenesis. This review explores miRNA modulators, focusing on ability to regulate associated cardiac fibrosis, hypertrophy, vascular inflammation. By bridging targeting, this highlights innovative pathways advancing treatment strategies. Additionally, preclinical clinical evidence supporting interactions is discussed, alongside challenges opportunities developing flavonoid-based therapies. Unlocking synergy could pave way more effective, personalized approaches management, addressing unmet needs contemporary cardiovascular care.

Language: Английский

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From small‐scale studies to an encompassing view: Inhibiting inflammation and clinically relevant enzymes with various extracts of Primula vulgaris using in vitro and in silico techniques

Food Frontiers, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 30, 2024

Abstract The genus Primula holds great importance as a source of traditional remedies in various folk medicine systems. In the present study, we investigated chemical composition and biological properties different extracts (ethyl acetate, ethanol, ethanol/water, water) aerial parts rhizomes vulgaris . To determine profile, were analyzed using ultrahigh performance liquid chromatography‐high‐resolution mass spectrometry (UHPLC‐HRMS) technique flavonoids major group this profile. antioxidant capacity was demonstrated by vitro tests general ethanol/water extract found to be most potent. Enzyme inhibition studied against enzymes ethanol more active than others. assess anti‐inflammatory potential at molecular level, human dermal fibroblasts (HDF) treated with lipopolysaccharide (LPS). experiments showed that levels nuclear factor kappa B (NFKB), receptor for advanced glycation endproducts (RAGE), activator protein‐1 (AP‐1), interleukin 6 (IL‐6), 17 (IL‐17) tumor necrosis (TNF)‐alpha significantly reduced after treatment tested extracts. addition, an inhibitory effect on collagenase, elastase, hyaluronidase, which are involved inflammatory process destabilization extracellular matrix (ECM). P. has been observed modulate metalloproteinase (MMP) synthesis decreasing concentration cellular reactive oxygen species (ROS) during LPS‐induced inflammation. This study also examined binding dynamic behavior proteins associated skin infections ligands derived from Simulations AutoDock Vina V1.1.2 GROMACS 2023.1 isoquercetin particular superior interactions hyaluronidase. These findings important development therapeutic strategies health infection control. summary, can considered natural bioactive compounds effective health‐promoting applications nutraceuticals, pharmaceuticals, cosmetics

Language: Английский

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Integrating UHPLC-Q-TOF-MS/MS, Network Pharmacology, Bioinformatics and Experimental Validation to Uncover the Anti-cancer Mechanisms of TiaoPi AnChang Decoction in Colorectal Cancer

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 334, P. 118576 - 118576

Published: July 14, 2024

Language: Английский

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Synergistic Mechanisms of Selected Polyphenols in Overcoming Chemoresistance and Enhancing Chemosensitivity in Colorectal Cancer

Antioxidants, Journal Year: 2024, Volume and Issue: 13(7), P. 815 - 815

Published: July 7, 2024

Colorectal cancer (CRC) is a leading cause of deaths worldwide. Despite significant advances in medical treatment, chemotherapy as monotherapy can lead to substantial side effects and chemoresistance. This underscores the need for therapeutic approaches that are not only pharmacologically safe but also modulate multiple potent signaling pathways sensitize cells overcome resistance standard drugs. In recent years, scientists have been searching natural compounds be used chemosensitizers addition conventional medications synergistic treatment CRC. Polyphenols represent diverse group target induce anti-cancer effects. Additionally, polyphenols shown work synergistically with chemotherapeutics other cells. review aims provide comprehensive insight into mechanisms selected CRC Further research clinical trials warranted fully harness combined or improving outcomes.

Language: Английский

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Discovery of flavopiridol as a noncovalent thioredoxin reductase inhibitor through in silico and in vitro approach

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 143641 - 143641

Published: April 1, 2025

Language: Английский

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Computational insights into the stereo-selectivity of catechins for the inhibition of the cancer therapeutic target EGFR kinase

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 11, 2024

The epidermal growth factor receptor (EGFR) plays a crucial role in regulating cellular and survival, its dysregulation is implicated various cancers, making it prime target for cancer therapy. Natural compounds known as catechins have garnered attention promising anticancer agents. These exert their effects through diverse mechanisms, primarily by inhibiting tyrosine kinases (RTKs), protein family that includes the notable member EGFR. Catechins, characterized two chiral centers stereoisomerism, demonstrate variations chemical physical properties due to differences spatial orientation of atoms. Although previous studies explored membrane fluidity transport across membranes, stereo-selectivity concerning EGFR kinase inhibition remains unexplored. In this study, we investigated kinase, both wild-type prevalent L858R mutant. Computational analyses indicated all stereoisomers, including extensively studied catechin (-)-EGCG, effectively bound within ATP-binding site, potentially activity. Notably, gallated emerged superior inhibitors non-gallated counterparts, revealing intriguing binding trends. top four stereoisomers exhibiting high dock scores energies with comprise (-)-CG (-)-GCG (+)-CG, (-)-EGCG. To assess dynamic behavior stability, molecular dynamics simulations over 100 ns were conducted top-ranked widely (-)-EGCG kinase. This study enhances our understanding how stereoisomeric nature drug influences inhibitory potential, providing insights could guide selection specific improved efficacy inexisting drugs.

Language: Английский

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Hydroxychloroquine interaction with phosphoinositide 3-kinase modulates prostate cancer growth in bone microenvironment: In vitro and molecular dynamics based approach

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 266, P. 130912 - 130912

Published: March 20, 2024

Language: Английский

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Exploring natural resources: Plumbagin as a potent anticancer agent

South African Journal of Botany, Journal Year: 2024, Volume and Issue: 174, P. 167 - 179

Published: Sept. 12, 2024

Language: Английский

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