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

Pansachon Intamalee,

Rungnapha Saeeng

и другие.

Drug Design Development and Therapy, Год журнала: 2025, Номер Volume 19, С. 3907 - 3924

Опубликована: Май 1, 2025

The COVID-19 pandemic, caused by SARS-CoV-2, highlights the urgent need for novel antiviral agents targeting key viral proteins. main protease (Mpro) is a crucial enzyme replication, making it an attractive drug target. Andrographolide, natural compound with known properties, serves as promising scaffold inhibitor development. This study aimed to design, synthesize, and evaluate C-12 dithiocarbamate andrographolide analogues potential SARS-CoV-2 Mpro inhibitors using computational experimental approaches. A structure-based design approach was employed derivatives. Molecular dynamics simulations were conducted assess binding interactions stability. hit synthesized evaluated inhibition assay against Mpro. Cytotoxicity assessed in HepG2, HaCaT, HEK293T cells determine safety profiles. Among designed compounds, 1, incorporating 2,4,5-trifluorobenzene moiety, exhibited strongest affinity stable residues (H41, M49 M165). Enzyme confirmed ~70% at 100 µM, moderate low cytotoxicity (CC50 values comparable andrographolide). Compound 1 represents non-covalent inhibitor. Further structural optimization necessary enhance potency, selectivity, therapeutic applications.

Язык: Английский

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

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 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.

Язык: Английский

Процитировано

2
Metabolomic and transcriptomic reveal flavonoid biosynthesis and regulation mechanism in Phlomoides rotata from different habitats DOI Creative Commons

Zuxia Li,

Guigong Geng,

Huichun Xie

и другие.

Genomics, Год журнала: 2024, Номер 116(3), С. 110850 - 110850

Опубликована: Апрель 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.

Язык: Английский

Процитировано

6
In Vitro Investigation of the Anti-Fibrotic Effects of 1-Phenyl-2-Pentanol, Identified from Moringa oleifera Lam., on Hepatic Stellate Cells DOI Open Access
Watunyoo Buakaew, Sucheewin Krobthong, Yodying Yingchutrakul

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(16), С. 8995 - 8995

Опубликована: Авг. 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

Язык: Английский

Процитировано

4
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

и другие.

Bioorganic Chemistry, Год журнала: 2025, Номер 159, С. 108343 - 108343

Опубликована: Март 9, 2025

Язык: Английский

Процитировано

0
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 Creative Commons
Kraikrit Utama, Nopawit Khamto, Atchara Janthong

и другие.

European Journal of Pharmacology, Год журнала: 2025, Номер unknown, С. 177636 - 177636

Опубликована: Апрель 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.

Язык: Английский

Процитировано

0
Design and Evaluation of Andrographolide Analogues as SARS-CoV-2 Main Protease Inhibitors: Molecular Modeling and in vitro Studies DOI Creative Commons
Utid Suriya,

Pansachon Intamalee,

Rungnapha Saeeng

и другие.

Drug Design Development and Therapy, Год журнала: 2025, Номер Volume 19, С. 3907 - 3924

Опубликована: Май 1, 2025

The COVID-19 pandemic, caused by SARS-CoV-2, highlights the urgent need for novel antiviral agents targeting key viral proteins. main protease (Mpro) is a crucial enzyme replication, making it an attractive drug target. Andrographolide, natural compound with known properties, serves as promising scaffold inhibitor development. This study aimed to design, synthesize, and evaluate C-12 dithiocarbamate andrographolide analogues potential SARS-CoV-2 Mpro inhibitors using computational experimental approaches. A structure-based design approach was employed derivatives. Molecular dynamics simulations were conducted assess binding interactions stability. hit synthesized evaluated inhibition assay against Mpro. Cytotoxicity assessed in HepG2, HaCaT, HEK293T cells determine safety profiles. Among designed compounds, 1, incorporating 2,4,5-trifluorobenzene moiety, exhibited strongest affinity stable residues (H41, M49 M165). Enzyme confirmed ~70% at 100 µM, moderate low cytotoxicity (CC50 values comparable andrographolide). Compound 1 represents non-covalent inhibitor. Further structural optimization necessary enhance potency, selectivity, therapeutic applications.

Язык: Английский

Процитировано

0