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

et al.

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

Published: May 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.

Language: Английский

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

et al.

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

Published: May 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.

Language: Английский

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