Computer-assisted discovery of natural inhibitors for platelet-derived growth factor alpha as novel therapeutics for thyroid cancer DOI Creative Commons

Hira Khalid,

Farah Sattar,

Iqra Ahmad

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 9, 2025

Platelet-derived growth factor alpha (PDGFRA) plays a significant role in various malignant tumors. PDGFRA expression boosts thyroid cancer cell proliferation and metastasis. Radiorefractory is poorly differentiated, very aggressive, resistant to radioiodine therapy. Thus, novel anticancer drugs that inhibit its metastasis are urgently required. In this context, we proposed the inhibitors by an optimized structure-based drug design approach. We performed virtual screening of metabolites derived from medicinal plants (Swertia chirayita, Myristica fragrans, Datura metel) successfully identified seven hits, namely cis-Grossamide K, Daturafoliside O, N-cis-feruloyltyramine, Maceneolignan H, Erythro-2-(4-allyl-2, 6-dimethoxyphenoxy)-1-(3, 4, 5-trimethoxyphenyl) propan-1, 3-diol, Myrifralignan C, stigmasteryl-3-O-β-glucoside as potential inhibitors. Not only top 7 hits exhibited higher docking scores simulation but also optimal drug-likeness non-toxic profiles pharmacokinetics analysis among 119 compounds. Our non-mutagenic, can cross blood-brain barrier, p-glycoprotein, while N-cis-feruloyltyramine has become lead compound. The protein-ligand stability 3 their interactions at binding site target protein were confirmed through molecular dynamic simulations. analyzed pharmacophoric features for stable active site. These candidates further characterized predict biological activity spectra human body characteristics know extensive behavior laboratory testing. This study necessitates in-vitro in-vivo studies confirm our discovery therapeutics against cancer.

Language: Английский

Computer-assisted discovery of natural inhibitors for platelet-derived growth factor alpha as novel therapeutics for thyroid cancer DOI Creative Commons

Hira Khalid,

Farah Sattar,

Iqra Ahmad

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 9, 2025

Platelet-derived growth factor alpha (PDGFRA) plays a significant role in various malignant tumors. PDGFRA expression boosts thyroid cancer cell proliferation and metastasis. Radiorefractory is poorly differentiated, very aggressive, resistant to radioiodine therapy. Thus, novel anticancer drugs that inhibit its metastasis are urgently required. In this context, we proposed the inhibitors by an optimized structure-based drug design approach. We performed virtual screening of metabolites derived from medicinal plants (Swertia chirayita, Myristica fragrans, Datura metel) successfully identified seven hits, namely cis-Grossamide K, Daturafoliside O, N-cis-feruloyltyramine, Maceneolignan H, Erythro-2-(4-allyl-2, 6-dimethoxyphenoxy)-1-(3, 4, 5-trimethoxyphenyl) propan-1, 3-diol, Myrifralignan C, stigmasteryl-3-O-β-glucoside as potential inhibitors. Not only top 7 hits exhibited higher docking scores simulation but also optimal drug-likeness non-toxic profiles pharmacokinetics analysis among 119 compounds. Our non-mutagenic, can cross blood-brain barrier, p-glycoprotein, while N-cis-feruloyltyramine has become lead compound. The protein-ligand stability 3 their interactions at binding site target protein were confirmed through molecular dynamic simulations. analyzed pharmacophoric features for stable active site. These candidates further characterized predict biological activity spectra human body characteristics know extensive behavior laboratory testing. This study necessitates in-vitro in-vivo studies confirm our discovery therapeutics against cancer.

Language: Английский

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