Cited by Design and Evaluation of Andrographolide Analogues as SARS-CoV-2 Main Protease Inhibitors: Molecular Modeling and in vitro Studies

Unveiling the antiviral inhibitory activity of ebselen and ebsulfur derivatives on SARS-CoV-2 using machine learning-based QSAR, LB-PaCS-MD, and experimental assay DOI

Silpsiri Sinsulpsiri, Yuji Nishii, Qing‐Feng Xu‐Xu

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 26, 2025

Ebsulfur and ebselen derivatives that were proven to be potent inhibitors against the main protease (MPro) of SARS-CoV-2 which is an essential enzyme for viral replication chosen study quantitative structure–activity relationship (QSAR) analysis using a classical multiple linear regression (MLR) machine learning approach random forest (RF) artificial neural network (ANN) in order find between molecular structural properties biological inhibitory activities. With statistical criteria, R2 values MLR, RF, ANN models training set 0.83, 0.82, 0.92, respectively. The RMSE test considered model evaluation, results 0.27, 0.18, 0.09 models, Therefore, was best-obtained predicting MPro activity thirteen new synthetic analogs haven't tested assay before. Notably, our predicted activities then examined enzyme-based assays cytotoxicity tests, found compound P8 resulted good potential candidate activity. Furthermore, dynamics simulations performed dynamic interaction ligand binding site; showed pathway mechanism with key residues surrounding active site MPro, useful further development derivatives.

Language: Английский

Citations

Metabolomic and transcriptomic reveal flavonoid biosynthesis and regulation mechanism in Phlomoides rotata from different habitats DOI

Zuxia Li,

Guigong Geng,

Huichun Xie

et al.

Genomics, Journal Year: 2024, Volume and Issue: 116(3), P. 110850 - 110850

Published: April 27, 2024

Phlomoides rotata is a traditional medical plant at 3100–5200 m altitude in the Tibet Plateau. In this study, flavonoid metabolites were investigated P. from Henan County (HN), Guoluo (GL), Yushu (YS), and Chengduo (CD) habitats Qinghai. The level of kaempferol 3-neohesperidoside, sakuranetin, biochanin A was high HN. content limocitrin isoquercetin YS. levels ikarisoside chrysosplenol D GL high. Schaftoside, miquelianin, malvidin chloride, glabrene CD exhibited levels. results showed significant correlation between 59 flavonoids 29 DEGs. Eleven increased with altitude. PAL2, UFGT6, COMT1, HCT2, 4CL4, HCT3 genes crucial regulating biosynthesis. Three enzymes CHS, 4CL, UFGT, This study provided biological chemical evidence for different uses various regional plants rotata.

Language: Английский

Citations

In Vitro Investigation of the Anti-Fibrotic Effects of 1-Phenyl-2-Pentanol, Identified from Moringa oleifera Lam., on Hepatic Stellate Cells DOI

Watunyoo Buakaew, Sucheewin Krobthong, Yodying Yingchutrakul

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 8995 - 8995

Published: Aug. 19, 2024

Liver fibrosis, characterized by excessive extracellular matrix deposition, is driven activated hepatic stellate cells (HSCs). Due to the limited availability of anti-fibrotic drugs, research on therapeutic agents continues. Here we have investigated

Language: Английский

Citations

Semi-synthetic flavonoid derivatives from Boesenbergia Rotunda induce extrinsic apoptosis pathway via Caspase-3 and Caspase-8 in HCT116 Colon Cancer cell lines DOI

Atchara Janthong, Kraikrit Utama, Nopawit Khamto

et al.

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: 159, P. 108343 - 108343

Published: March 9, 2025

Language: Английский

Citations

Discovery of Cinnamoyl–Flavonoid Hybrid Derivatives as Inhibitors of SARS-CoV-2 Mpro and Anti-inflammatory Agents: Experimental and In Silico Insights into their Efficacy against Lipopolysaccharide-Induced Lung Injury DOI

Kraikrit Utama, Nopawit Khamto, Atchara Janthong

et al.

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177636 - 177636

Published: April 1, 2025

The chemical structures of the parental compounds flavonoids from Boesenbergia rotunda were modified by conjugation with cinnamic acid to form cinnamoyl-flavonoid hybrid derivatives enhanced anti-inflammatory and SARS-CoV-2 Mpro-inhibitory properties. Cinnamoyl-flavonoid 6 10 showed potential inhibit Mpro IC50 values 52.49 22.62 μM. Compounds lower cytotoxicity in human lung cell lines MRC-5 A549 at concentrations greater than 50 effects on viability studied a 3D co-culture model treated lipopolysaccharide (LPS) observed through confocal microscopy. downregulated p65 mRNA expression, resulting reduction pro-inflammatory cytokines, including Interleukin 8 (IL-8) Monocyte Chemoattractant Protein-1 (MCP-1/CCL2), leading an response Nuclear factor kappa-light-chain-enhancer activated B cells (NF-κB) signalling pathways. Compound activity, downregulating Bcl-2 Associated X gene (BAX), which resulted inhibition apoptotic death when compared compound 10. In silico molecular dynamic simulation shed light how these interact myeloid differentiation 2 (MD-2), is involved inflammatory response. Our findings suggest that show as drugs anti-SARS-CoV-2 drugs.

Language: Английский

Citations

Design and Evaluation of Andrographolide Analogues as SARS-CoV-2 Main Protease Inhibitors: Molecular Modeling and in vitro Studies DOI

Utid Suriya,

Pansachon Intamalee,

Rungnapha Saeeng

et al.

Drug Design Development and Therapy, Journal Year: 2025, Volume and Issue: Volume 19, P. 3907 - 3924

Published: May 1, 2025

Language: Английский

Citations