Previtali, Viola;Mihigo, Helene B.;Amet, Rebecca;McElligott, Anthony M.;Zisterer, Daniela M.;Rozas, Isabel published 《Exploring the anti-cancer mechanism of novel 3,4′-substituted diaryl guanidinium derivatives》 in 2020. The article was appeared in 《Pharmaceuticals》. They have made some progress in their research.Recommanded Product: 2657-87-6 The article mentions the following:
We previously identified a guanidinium-based lead compound that inhibited BRAF through a hypothetic type-III allosteric mechanism. Considering the pharmacophore identified in this lead compound (i.e., “lipophilic group”, “di-substituted guanidine”, “phenylguanidine polar end”), several modifications were investigated to improve its cytotoxicity in different cancer cell lines. Thus, several lipophilic groups were explored, the di-substituted guanidine was replaced by a secondary amine and the Ph ring in the polar end was substituted by a pyridine. In a structure-based design approach, four representative derivatives were docked into an inhouse model of an active triphosphate-containing BRAF protein, and the interactions established were analyzed. Based on these computational studies, a variety of derivatives was synthesized, and their predicted drug-like properties calculated Next, the effect on cell viability of these compounds was assessed in cell line models of promyelocytic leukemia and breast, cervical and colorectal carcinomas. The potential of a selection of these compounds as apoptotic agents was assessed by screening in the promyelocytic leukemia cell line HL-60. The toxicity against non-tumorigenic epithelial MCF10A cells was also investigated. These studies allowed for several structure-activity relationships to be derived. Investigations on the mechanism of action of representative compounds suggest a divergent effect on inhibition of the MAPK/ERK signaling pathway. The experimental procedure involved many compounds, such as 3-(4-Aminophenoxy)aniline (cas: 2657-87-6) .
3-(4-Aminophenoxy)aniline is one of ethers-buliding-blocks. Ethers feature bent C–O–C linkages. In dimethyl ether, the bond angle is 111° and C–O distances are 141 pm. The barrier to rotation about the C–O bonds is low. Recommanded Product: 2657-87-6 The bonding of oxygen in ethers, alcohols, and water is similar. In the language of valence bond theory, the hybridization at oxygen is sp3.
Reference:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem