Targeting Yes‐Associated Protein (YAP) in Breast Cancer: In Silico Molecular Dynamics, Luminescence‐Based In Vitro, and In Vivo Validation of Rauvolfia tetraphylla‐Derived Inhibitors DOI

B. Balavaishnavi,

M. Kamaraj,

T. G. Nithya

et al.

Luminescence, Journal Year: 2024, Volume and Issue: 39(12)

Published: Dec. 1, 2024

ABSTRACT The study aims to elucidate the pharmacological mechanism of Rauvolfia tetraphylla against breast cancer through a comprehensive, multi‐faceted approach. This includes molecular docking, dynamics, and experimental validation. Initial screening via ADME analysis network pharmacology identified key compounds potential targets. Protein–protein interaction (PPI) pinpointed Yes‐associated protein‐1 (YAP) as crucial target. Molecular docking revealed that three compounds—ajmaline, reserpine, serpentine—exhibited strong binding affinities with YAP, scores −6.5 −6.7 kcal/mol. dynamics simulations were conducted assess stability these interactions further. Experimental validation showed R. inhibited cell proliferation, an IC50 348.69 μg/mL, while demonstrating cytoprotective effects on Vero cells (IC50: 1056.23 μg/mL). Migration assays indicated 88.5% reduction in migration, increased ROS levels signaled elevated stress cells. Apoptosis was confirmed by AO/EtBr staining. In vivo DMBA‐induced mouse model significant tumor growth inhibition, supported changes YAP expression histopathological analysis. These findings highlight promising therapeutic candidate cancer, offering insights into its mechanisms for future drug development clinical applications.

Language: Английский

Network Analysis and Computer-Aided Drug Design Targeting the Acetyl Cholinesterase Pathway in Alzheimer's Disease: Unlocking Novel Therapeutic Strategies DOI

Enamul Kabir Talukder,

Md Aktaruzzaman, Foysal Ahammad

et al.

Published: Jan. 1, 2024

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Language: Английский

Citations

0
Insight into Binding and Interaction of Docking, Dynamics and Network Pharmacology to Explore the Target on Cancer Inhibitors DOI

Ekambaram Gayathiri,

Palanisamy Prakash, Thangaraj Pratheep

et al.

Journal of Pharmaceutical Innovation, Journal Year: 2024, Volume and Issue: 19(5)

Published: Aug. 27, 2024

Language: Английский

Citations

0
Targeting Yes‐Associated Protein (YAP) in Breast Cancer: In Silico Molecular Dynamics, Luminescence‐Based In Vitro, and In Vivo Validation of Rauvolfia tetraphylla‐Derived Inhibitors DOI

B. Balavaishnavi,

M. Kamaraj,

T. G. Nithya

et al.

Luminescence, Journal Year: 2024, Volume and Issue: 39(12)

Published: Dec. 1, 2024

ABSTRACT The study aims to elucidate the pharmacological mechanism of Rauvolfia tetraphylla against breast cancer through a comprehensive, multi‐faceted approach. This includes molecular docking, dynamics, and experimental validation. Initial screening via ADME analysis network pharmacology identified key compounds potential targets. Protein–protein interaction (PPI) pinpointed Yes‐associated protein‐1 (YAP) as crucial target. Molecular docking revealed that three compounds—ajmaline, reserpine, serpentine—exhibited strong binding affinities with YAP, scores −6.5 −6.7 kcal/mol. dynamics simulations were conducted assess stability these interactions further. Experimental validation showed R. inhibited cell proliferation, an IC50 348.69 μg/mL, while demonstrating cytoprotective effects on Vero cells (IC50: 1056.23 μg/mL). Migration assays indicated 88.5% reduction in migration, increased ROS levels signaled elevated stress cells. Apoptosis was confirmed by AO/EtBr staining. In vivo DMBA‐induced mouse model significant tumor growth inhibition, supported changes YAP expression histopathological analysis. These findings highlight promising therapeutic candidate cancer, offering insights into its mechanisms for future drug development clinical applications.

Language: Английский

Citations

0