《Drug-like biimidazole derivatives dually target c-MYC/BCL-2 G-quadruplexes and inhibit acute myeloid leukemia》 was published in Bioorganic Chemistry in 2020. These research results belong to Hu, Ming-Hao; Yu, Bing-Ying; Wang, Xiaodong; Jin, Guangyi. Formula: C5H12N2 The article mentions the following:
Chemotherapy is the main approach for treating acute myeloid leukemia (AML). However, this therapy can cause severe side effects as well as drug resistance, hence calling for new therapeutic strategies. As c-MYC and BCL-2 are often overexpressed in AML, and synergism between c-MYC and BCL-2 promotes tumorigenesis, therefore, dual targeting of c-MYC/BCL-2 promoter G-quadruplexes (G4s) and then inhibiting the targeted gene expression would be a potential strategy in ALM treatment. In this work, in the search of dual ligands, we performed a screening assay with an inhouse, imidazole-based compound library. Consequently, two drug-like biimidazole derivatives were identified as selective c-MYC/BCL-2 G4 binders, of which, BIM-2 was selected as the candidate for inhibiting AML cell growth. Then, BIM-2 was demonstrated to downregulate both c-MYC and BCL-2 expression, and thereby cause cell cycle arrest at G0/G1 phase and apoptosis in AML cells. Furthermore, the possible end-stacking binding modes between BIM-2 and c-MYC/BCL-2 G4s were revealed by NMR and mol. docking studies. Accordingly, this study provides a new class of drug-like dual-selective c-MYC/BCL-2 G4 ligands for the potential treatment of AML. In the part of experimental materials, we found many familiar compounds, such as 1-Methylpiperazine(cas: 109-01-3Formula: C5H12N2)
1-Methylpiperazine(cas: 109-01-3) can be used as mimic template in the preparation of molecularly imprinted microspheres (MIMs). It was also used to prepare the difunctional strong anion-exchange stationary phase from a 1,4-diazacyclohexane derivative..Formula: C5H12N2
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics