Chemistry can be defined as the study of matter and the changes it undergoes. You¡¯ll sometimes hear it called the central science because it is the connection between physics and all the other sciences, starting with biology. 611-73-4, Name is 2-Oxo-2-phenylacetic acid, molecular formula is , belongs to phthalazines compound. In a document, author is Reilly, Sean W., Name: 2-Oxo-2-phenylacetic acid.
Examination of Diazaspiro Cores as Piperazine Bioisosteres in the Olaparib Framework Shows Reduced DNA Damage and Cytotoxicity
Development of poly(ADP-ribose) polymerase inhibitors (PARPi’s) continues to be an attractive area of research due to synthetic lethality in DNA repair deficient cancers; however, PARPi’s also have potential as therapeutics to prevent harmful inflammation. We investigated the pharmacological impact of incorporating spirodiamine motifs into the phthalazine architecture of FDA approved PARPi olaparib. Synthesized analogues were screened for PARP-1 affinity, enzyme specificity, catalytic inhibition, DNA damage, and cytotoxicity. This work led to the identification of 10e (12.6 +/- 1.1 nM), which did not induce DNA damage at similar drug concentrations as olaparib. Interestingly, several worst in class compounds with low PARP-1 affinity, including 15b (4397 +/- 1.1 nM), induced DNA damage at micromolar concentrations, which can explain the cytotoxicity observed in vitro. This work provides further evidence that high affinity PARPi’s can be developed without DNA damaging properties offering potential new drugs for treating inflammatory related diseases.
If you are hungry for even more, make sure to check my other article about 611-73-4, Name: 2-Oxo-2-phenylacetic acid.
Reference:
Phthalazine – Wikipedia,
,Phthalazine | C8H6N2 – PubChem