A variety of diseases, including the development of several cancers, are caused by the interruption of protein kinases' normal activity. For the creation of anticancer medications, inhibition of the activity of the particular protein kinases continues to be a key target. Utilizing a variety of substituted purines and 3-(trifluoromethyl)phenyl, a novel class of putative protein kinase inhibitors 7–16 was synthesised in high yields.
In this work, the 3-(trifluoromethyl)phenyl moiety was left unreplaced while purine derivatives were connected through the N-9 atom to the methyl group of 4-methylbenzamide. Since purine is a component of ATP, it has the potential to create the required hydrogen bonds in the ATP-pocket of protein kinase. The bulk of known inhibitors contain 3-(trifluoromethyl)aniline, which is also known to have strong affinity for the kinase's allosteric site. Targeted structures, on the other hand, might be categorised as modified nucleosides where the sugar portion has been replaced with 4-methylbenzamide.
Similar to the results for sorafenib, the most promising compounds 7 and 10, which included chlorine atoms in the purine heterocycle's C-2 and C-6 locations, shown inhibitory efficacy against seven cancer cell lines. Compounds 7 and 10 had IC50 values for K562 cells of 2.27 M and 2.53 M, HL-60 cells of 1.42 M and 1.52 M, and OKP-GS cells of 4.56 M and 24.77 M, respectively. Additionally, chemicals 7 and 10 dose-dependently caused apoptosis and a G2/M phase cell cycle arrest in OKP-GS cells, halting cell division. At a concentration of 1 M, compounds 7, 9, and 10 exhibited 36 to 45 percent inhibitory action against PDGFR and PDGFR.
The findings of docking and molecular dynamics revealed that the named compounds' structures are made more favourable by the addition of a 4-methylimidazole fragment.
Author(s) Details:
Elena Kalinichenko,
Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus,
BY-220141, 5/2 Academician V.F. Kuprevich Street, Minsk, Belarus.
Aliaksandr Faryna,
Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus,
BY-220141, 5/2 Academician V.F. Kuprevich Street, Minsk, Belarus.
Tatyana Bozhok,
Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus,
BY-220141, 5/2 Academician V.F. Kuprevich Street, Minsk, Belarus.
Alesya Panibrat,
Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus,
BY-220141, 5/2 Academician V.F. Kuprevich Street, Minsk, Belarus.
Please see the link here:
https://stm.bookpi.org/CTCB-V4/article/view/7813
No comments:
Post a Comment