Bioactive Indanes: Design, synthesis and bioactivity investigation of 2,2-substituted Indane derivatives, a new bioactive Indane scaffold DOI Creative Commons
Tao Zhang, Kit Yee Chan, Abdulilah Ece

et al.

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: 159, P. 108352 - 108352

Published: March 9, 2025

The indane scaffold, prevalent in bioactive natural products, underpins numerous therapeutics. Our group developed a series of 1,2-indane dimers, including PH46A (9), for inflammatory and autoimmune diseases. This study details the design, synthesis characterisation 21 compounds, 2,2-disubstituted indanones (16a-16h), indanols (17a-17h), indanes (18a-18h). These compounds were tested vitro vivo using murine dextran sulphate sodium (DSS) model bowel disease (IBD). Cytotoxicity screening THP-1 macrophages SW480 cells revealed increased cytotoxicity with indene ring substitution at C2, 18d emerging as potent. In lipoxygenase (LOX) assays, 18a, 18d, 18c exhibited significant 5-LOX inhibition, comparable to zileuton. Selective inhibition over 15-LOX indicated distinct ligand-isozyme interactions, potentially informing novel inhibitor development. Cytokine profiling identified optimal C1 C2 substituents, particularly which inhibited IL-6, IL-1β, TNF-α, IFN-γ IL-8 cells. DSS colitis testing showed activity index reduction (p < 0.01) 18d. Subsequent molecular docking, docking simulations predicted stable binding under mimicked physiological conditions. findings offer insights into indane-based therapeutic drug development IBD, highlighting cost reductions by minimising stereochemistry complexity.

Language: Английский

Anti-alzheimer's Disease Properties of Vanillic Acid-thiazole Hybrids: Synthesis, Characterization, and Biological Evaluation DOI

Zhao‐Yuan Zhang,

Shu‐Tong Han,

Jiliang Hu

et al.

Journal of Molecular Structure, Journal Year: 2025, Volume and Issue: 1328, P. 141378 - 141378

Published: Jan. 8, 2025

Language: Английский

Citations

1
Bioactive Indanes: Design, synthesis and bioactivity investigation of 2,2-substituted Indane derivatives, a new bioactive Indane scaffold DOI Creative Commons
Tao Zhang, Kit Yee Chan, Abdulilah Ece

et al.

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: 159, P. 108352 - 108352

Published: March 9, 2025

The indane scaffold, prevalent in bioactive natural products, underpins numerous therapeutics. Our group developed a series of 1,2-indane dimers, including PH46A (9), for inflammatory and autoimmune diseases. This study details the design, synthesis characterisation 21 compounds, 2,2-disubstituted indanones (16a-16h), indanols (17a-17h), indanes (18a-18h). These compounds were tested vitro vivo using murine dextran sulphate sodium (DSS) model bowel disease (IBD). Cytotoxicity screening THP-1 macrophages SW480 cells revealed increased cytotoxicity with indene ring substitution at C2, 18d emerging as potent. In lipoxygenase (LOX) assays, 18a, 18d, 18c exhibited significant 5-LOX inhibition, comparable to zileuton. Selective inhibition over 15-LOX indicated distinct ligand-isozyme interactions, potentially informing novel inhibitor development. Cytokine profiling identified optimal C1 C2 substituents, particularly which inhibited IL-6, IL-1β, TNF-α, IFN-γ IL-8 cells. DSS colitis testing showed activity index reduction (p < 0.01) 18d. Subsequent molecular docking, docking simulations predicted stable binding under mimicked physiological conditions. findings offer insights into indane-based therapeutic drug development IBD, highlighting cost reductions by minimising stereochemistry complexity.

Language: Английский

Citations

0