Design, synthesis, and biological evaluation of novel diphenylamine derivatives as tubulin polymerization inhibitors targeting the colchicine binding site was written by Yan, Xiang-Yu;Leng, Jia-Fu;Chen, Ting-Ting;Zhao, Yong-Jun;Kong, Ling-Yi;Yin, Yong. And the article was included in European Journal of Medicinal Chemistry in 2022.Safety of 4-Bromo-2,6-difluoroanisole This article mentions the following:
A novel series of diphenylamine derivatives were designed and synthesized I and their biol. activities were evaluated. The anti-proliferative activities of the derivatives were tested against five human cancer cell lines (MCF-7, MDA-MB-231, A549, HeLa and HT29). Among them, I exhibited the promising anti-proliferative activity against HT29 cell lines with the IC50 value of 23 nM. Further biol. studies depicted that I inhibited cancer cell migration, colony formation and angiogenesis. Besides, dynamics studies and mol. docking studies revealed that I inhibited tubulin polymerization which may be a result of the compound binding to the colchicine site of tubulin. Furthermore,I arrested HT29 cell cycle at G2/M phase, and induced HT29 cell apoptosis by upregulating cyclin B1, Bcl-2, Bax, Cleaved-caspase9, Cleaved-caspase3, PARP, Cleaved-PARP proteins, and downregulating p-cdc25c (S216), p-cdc2 (T15) proteins. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were also determined to confirm the cell apoptosis process. Finally, I greatly inhibited the tumor growth in HT29 xenograft mice by 75.5% at 10 mg/kg. Meanwhile, I owned the good pharmacokinetic properties. All the results promised that I is of potential to act as an antitumor candidate and worthy of further investigation. In the experiment, the researchers used many compounds, for example, 4-Bromo-2,6-difluoroanisole (cas: 104197-14-0Safety of 4-Bromo-2,6-difluoroanisole).
4-Bromo-2,6-difluoroanisole (cas: 104197-14-0) belongs to ethers. Ether is less polar than esters, alcohols or amines because of the oxygen atom that is unable to participate in hydrogen bonding due to the presence of bulky alkyl groups on both sides of the oxygen atom. At room temperature, ethers are pleasant-smelling colourless liquids. Relative to alcohols, ethers are generally less dense, are less soluble in water, and have lower boiling points. They are relatively unreactive, and as a result they are useful as solvents for fats, oils, waxes, perfumes, resins, dyes, gums, and hydrocarbons. Vapours of certain ethers are used as insecticides, miticides, and fumigants for soil.Safety of 4-Bromo-2,6-difluoroanisole
Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem