New Quinoxaline-Based Derivatives as PARP-1 Inhibitors: Design, Synthesis, Antiproliferative, and Computational Studies.

ABSTRACT: Herein, 2,3-dioxo-1,2,3,4-tetrahydroquinoxaline was used as a bio-isosteric scaffold to the phthalazinone motif of the standard drug Olaparib to design and synthesize new derivatives of potential PARP-1 inhibitory activity using the 6-sulfonohydrazide analog 3 as the key intermediate. Although the new compounds represented the PARP-1 suppression impact of IC₅₀ values in the nanomolar range, compounds 8a, 5 were the most promising suppressors, producing IC₅₀ values of 2.31 and 3.05 nM compared to Olaparib with IC₅₀ of 4.40 nM. Compounds 4, 10b, and 11b showed a mild decrease in the potency of the IC₅₀ range of 6.35-8.73 nM. Furthermore, compounds 4, 5, 8a, 10b, and 11b we

SUBMITTER: Syam YM 

PROVIDER: S-EPMC9370283 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature