Design, synthesis, and multi-target anticancer evaluation of 1,3-thiazolodin-4-one analogues against breast cancer: mechanistic insights into estrogen metabolism, inflammation, angiogenesis, and oxidative stress
Abstract
toxicity profiling predicted a favorable safety profile, with no Ames mutagenicity, no hERG inhibition, no skin sensitization, low acute/chronic toxicity, and no predicted CYP450 inhibition. ProTox-III classified compound 6 as inactive toward major organ-toxicity endpoints. Computational studies supported these results: docking and 100-ns MD simulations showed stable binding to aromatase, STS, COX-2, TNF-α, and VEGFR-II. PCA and free-energy landscape analyses revealed early conformational adjustments followed by convergence into compact, low-energy states, consistent with stable ligand-protein interactions. Overall, compound 6 emerges as a promising multitarget lead integrating cytotoxic, hormone-modulatory, anti-inflammatory, antioxidant, and anti-angiogenic activities for potential breast cancer therapy.
Fields of Study & Subjects
Estrogen and related hormone effects
Synthesis and biological activity
Cytokine Signaling Pathways and Interactions
Publication details
- Journal / source
- RSC Advances
- Publisher
- Royal Society of Chemistry (RSC)
- Volume
- 16
- Issue
- 3
- Pages
- 2528–2554
- Publication date
- 1 January 2026
- Language
- EN