Design and Computational Study of Sulfonamide-Modified Cannabinoids as Selective COX-2 Inhibitors Using Semiempirical Quantum Mechanical Methods: Drug-like Properties and Binding Affinity Insights DOI Creative Commons

Watcharin Kumaeum,

Panichakorn Jaiyong

ACS Omega, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

Cyclooxygenase (COX) is one of the concerned targets in development anti-inflammatory therapies. Using semiempirical quantum mechanical (SQM) methods with implicit solvation, we investigated binding free energies and selectivity natural cannabinoids their sulfonamide-modified derivatives COX cannabinoid (CB) receptors. Validation against benchmark data sets demonstrated accuracy these predicting affinities while minimizing false positives negatives often associated conventional docking tools. Our findings indicate that Δ9-THC its carboxylic acid derivative exhibit strong for COX-2 CB2, suggesting potential as agents, though significant CB1 affinity suggests psychoactive risks. In contrast, such CBCA, CBNA, CBEA, CBTA, CBLA selective to low affinity, supporting promising leads reduced side effects. Sulfonamide-modified analogs further enhanced selectivity, displaying favorable drug-like properties, including compliance Lipinski's rules, noninhibition cytochromes P450, oral bioavailability. These results highlight utility GFN2-xTB identifying optimizing cannabinoid-based therapeutic candidates applications.

Language: Английский

Synthetic and plant-derived multivalent galactans as modulators of cancer-associated galectins-3 and -9 DOI Open Access
Lukáš Pfeifer,

Kim‐Kristine Mueller,

M. Müller

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 19, 2025

Abstract Galectins are β-galactoside-binding proteins with numerous functions. Some of them involved in proliferation and metastasis cancer, making promising therapeutic targets. As different plant glycans have been shown to bind galectins, saccharides might be potential galectin inhibitors. To produce galactans rich galactose smaller size, we degraded arabinogalactan-proteins from Echinacea purpurea Zostera marina as well arabinogalactan larch. (Gal)-3 -9 both described cancer development, quantified the binding capacities galectins by biolayer-interferometry. Our results revealed that all plant-derived Yariv reagents terminal lactose residues Gal-3 micromolar ranges. Surprisingly, only higher charged showed affinity Gal-9. Investigations two pancreatic cell lines (Panc1 Panc89) variants thereof was expressed a significantly level Panc1 cells compared Panc89 cells. Conversely, Gal-9 detected The findings sources develop antagonists species express specificities for distinct galectins.

Language: Английский

Citations

0
Synthetic and plant-derived multivalent galactans as modulators of cancer-associated galectins-3 and -9 DOI Creative Commons
Lukáš Pfeifer,

Kim‐Kristine Mueller,

M. Müller

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: 305, P. 141155 - 141155

Published: Feb. 18, 2025

Language: Английский

Citations

0
Design and Computational Study of Sulfonamide-Modified Cannabinoids as Selective COX-2 Inhibitors Using Semiempirical Quantum Mechanical Methods: Drug-like Properties and Binding Affinity Insights DOI Creative Commons

Watcharin Kumaeum,

Panichakorn Jaiyong

ACS Omega, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

Cyclooxygenase (COX) is one of the concerned targets in development anti-inflammatory therapies. Using semiempirical quantum mechanical (SQM) methods with implicit solvation, we investigated binding free energies and selectivity natural cannabinoids their sulfonamide-modified derivatives COX cannabinoid (CB) receptors. Validation against benchmark data sets demonstrated accuracy these predicting affinities while minimizing false positives negatives often associated conventional docking tools. Our findings indicate that Δ9-THC its carboxylic acid derivative exhibit strong for COX-2 CB2, suggesting potential as agents, though significant CB1 affinity suggests psychoactive risks. In contrast, such CBCA, CBNA, CBEA, CBTA, CBLA selective to low affinity, supporting promising leads reduced side effects. Sulfonamide-modified analogs further enhanced selectivity, displaying favorable drug-like properties, including compliance Lipinski's rules, noninhibition cytochromes P450, oral bioavailability. These results highlight utility GFN2-xTB identifying optimizing cannabinoid-based therapeutic candidates applications.

Language: Английский

Citations

0