In Silico Discovery of Multi-Target Natural Ligands and Efficient siRNA Design for Overcoming Drug Resistance in Breast Cancer via Local Therapy DOI Open Access

Seyed Mohammad Javad Hashemi,

Ali Barzegar, Javad Akhtari

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 11, 2024

Abstract In this study, we designed an efficient siRNA for PKMYT1 gene knockdown, and evaluated the binding affinities of different natural ligands to crucial proteins involved in breast cancer. Designed showed strong affinity minimal off-target effects. Molecular docking studies identified new as antagonists with high aromatase, estrogen receptor alpha, HER2, PARP10, well agonists MT2 STING. The ligand SCHEMBL7562664 was introduced a golden due its among multiple targets lack cytotoxic mutagenic Natural small molecules research, their multi-target characteristics, provided solution overcome problem drug resistance cancer cells. Furthermore, proposed three dimensional scaffold design local therapy offers promising approach increase delivery efficacy these molecules, reduce systemic side effects, improve treatment outcomes. significant favorable pharmacokinetic properties were identified, which paves way further research targeted

Language: Английский

Melatonin and the Skin: Current Progress and Perspectives for Human Health DOI
Andrzej Słomiński, Tae Kim, Zorica Janjetović

et al.

Journal of Investigative Dermatology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

1
Melatonin as an adjunctive therapy in cardiovascular disease management DOI Creative Commons

Zan Luo,

Yuan Tang,

Liang Zhou

et al.

Science Progress, Journal Year: 2024, Volume and Issue: 107(4)

Published: Oct. 1, 2024

Melatonin, N-acetyl-5-methoxytryptamine, is a neuroendocrine hormone secreted by the pineal gland. This pleiotropic indoleamine possesses amphiphilic properties, allowing it to penetrate most biological barriers and exert its effects at subcellular level. Importantly, melatonin also plays crucial role in regulating body's response circadian rhythms, adapting internal external environmental cues. Melatonin functions as powerful antioxidant free radical scavenger, protecting cells from oxidative damage. Its diverse physiological roles include maintaining functional integrity of endothelial cells, thereby preventing atherosclerosis, major contributor cardiovascular disease. Additionally, exhibits scavenging potentially improving metabolic disorders. These combined suggest unique adjunctive therapeutic potential for treating diseases. review aims explore mechanisms which interacts with system investigates use an agent managing

Language: Английский

Citations

4
IN SILICO STUDIES AND CYTOTOXICITY ASSAY OF BENZYLIDENE BENZO HYDRAZIDE DERIVATIVES ON CANCER STEM CELL DOI Open Access
Imanuel Gauru,

Yusuf Syahril Alam,

Mardi Santoso

et al.

International Journal of Applied Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown, P. 134 - 141

Published: March 7, 2025

Objective: This study aimed to evaluate the biological activity of benzylidene benzohydrazide derivatives against Cancer Stem Cells (CSCs) through in vitro cytotoxicity tests and silico analyses using molecular docking. Methods: Four hydrazone compounds, namely benzo hydrazide (L1), 2-methyl (L2), 2-nitro (L3), 2-bromobenzylidene (L4) were used for studies. The interaction between compounds EGFR protein receptor (PDB ID: 1m17) was investigated AutoDock tools 1.5.7. PASS server predicted activities substances. ADMET assessed ADMETLab 2.0. Meanwhile, cytotoxic test on CSCs evaluated MTT Assay method. Results: results docking analysis L1-L4 provide binding energy values ranging from -6.69 to-7.74 kcal/mol. value is lower than reference Doxorubicin (-4.30 Kcal/mol). with IC50 L1 0.220±0.360 μg/ml, L2 0.034±0.023 L3 0.355±0.276 L4 1.193±1.122 μg/ml 0.220±0.180 μg/ml. These indicate that have potential be inhibitor. Conclusion: (L2) had as a inhibitor vigorous cell lines

Language: Английский

Citations

0
In Silico Discovery of Multi-Target Natural Ligands and Efficient siRNA Design for Overcoming Drug Resistance in Breast Cancer via Local Therapy DOI Open Access

Seyed Mohammad Javad Hashemi,

Ali Barzegar, Javad Akhtari

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 11, 2024

Abstract In this study, we designed an efficient siRNA for PKMYT1 gene knockdown, and evaluated the binding affinities of different natural ligands to crucial proteins involved in breast cancer. Designed showed strong affinity minimal off-target effects. Molecular docking studies identified new as antagonists with high aromatase, estrogen receptor alpha, HER2, PARP10, well agonists MT2 STING. The ligand SCHEMBL7562664 was introduced a golden due its among multiple targets lack cytotoxic mutagenic Natural small molecules research, their multi-target characteristics, provided solution overcome problem drug resistance cancer cells. Furthermore, proposed three dimensional scaffold design local therapy offers promising approach increase delivery efficacy these molecules, reduce systemic side effects, improve treatment outcomes. significant favorable pharmacokinetic properties were identified, which paves way further research targeted

Language: Английский

Citations

0