Synthesis and biological evaluation of biaryl compounds as PD-L1 and c-MYC inhibitors

Abstract

The main aim of this project is the search for compounds with dual inhibitory activity on cMYC and PD-L1. Following the recent publication focused on the use of biaryl derivatives as small-molecule inhibitors of cancer-related proteins, the research group I have worked with is carrying out a line of research on the development of derivatives of arylpyridines and arylpyrimidines as chemical inhibitors of c-MYC and PD-L1 proteins. Therefore, it has been decided to synthesize (methoxyphenyl)pyridine and (methoxyphenyl)pyrimidine derivative compounds because previous results obtained within the research group showed that similar biaryl derivatives had significant inhibitory activity on PD-L1 and c-MYC. Thus, the aims of this project are: 1. Synthesis of the biaryl compounds depicted in Figure 12. 2. Biologic evaluation of the selected compounds: 2.1. Study of the antiproliferative activity and cytotoxicity by MTT assay. 2.2. Study of the interaction of compounds with PD-L1 by Protein Thermal Shift assay. 2.3. Study of the effect on c-MYC and PD-L1 in tumor cells by flow cytometry assay. 2.4. Cell co-cultures assays.