1,2,4-Oxadiazole-5-ones as analogues of tamoxifen: synthesis and biological evaluation
Abstract
A series of 2,3,4-triaryl-substituted 1,2,4-oxadiazole-5-ones have been prepared as fixed-ring analogues of tamoxifen (TAM), a drug inhibitor of Estradiol Receptor (ER) used in breast cancer therapy, by an efficient synthetic protocol based on a 1,3-dipolar cycloaddition of nitrones to isocyanates. Some of the newly synthesized compounds (14d-f, 14h and 14k) show a significant cytotoxic effect in a human breast cancer cell line (MCF-7) possessing IC50 values between 15.63 and 31.82 μM. In addition, compounds 14d-f, 14h and 14k are able to increase the p53 expression levels, activating also the apoptotic pathway. Molecular modeling studies of novel compounds performed on the crystal structure of ER reveal the presence of strong hydrophobic interactions with the aromatic rings of the ligands similar to TAM. These data suggest that 1,2,4-oxadiazole-5-ones can be considered analogues of TAM, and that their anticancer activity might be partially due to ER inhibition.
Read the paper
Related studies
- Quantum dots: synthesis, bioapplications, and toxicity
- A Guide to In Silico Drug Design
- Quantum Computing for Healthcare: A Review
- Automated in Silico Design of Homogeneous Catalysts
- Identification of Novel 3-Hydroxy-pyran-4-One Derivatives as Potent HIV-1 Integrase Inhibitors Using in silico Structure-Based Combinatorial Library Design Approach
- In silico structural elucidation of RNA-dependent RNA polymerase towards the identification of potential Crimean-Congo Hemorrhagic Fever Virus inhibitors
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.