Synthesis and evaluation of 2-(4-[4-acetylpiperazine-1-carbonyl] phenyl)-1H-benzo[d]imidazole-4-carboxamide derivatives as potential PARP-1 inhibitors and preliminary study on structure-activity relationship was written by Chen, Miaojia;Huang, Honglin;Wu, Kaiyue;Liu, Yunfan;Jiang, Lizhi;Li, Yang;Tang, Guotao;Peng, Junmei;Cao, Xuan. And the article was included in Drug Development Research in 2022.Category: imidazoles-derivatives This article mentions the following:
A series of 2-(4-[4-substitutedpiperazine-1-carbonyl]phenyl)-1H-benzo[d]imidazole-4-carboxamide derivatives I [R = Me, Ph, 2-furyl, etc.] was designed, synthesized and successful characterization as novel and effective poly ADP-ribose polymerases (PARP)-1 inhibitors to improve the structure-activity relationships about the substituents in the hydrophobic pocket. These derivatives were evaluated for their PARP-1 inhibitory activity and cellular inhibitory against BRCA-1 deficient cells (MDA-MB-436) and wild cells (MCF-7) using PARP kit assay and MTT method. The results indicated that compared with other heterocyclic compounds, furan ring-substituted derivatives I [R = 2-furyl, 3-methyl-2-furyl, 5-bromo-2-furyl, 5-chloro-2-furyl] showed better PARP-1 inhibitory activity. Among this derivatives, compound I [R = 5-bromo-2-furyl] displayed the strongest inhibitory effects on PARP-1 enzyme (IC50 = 0.023渭M), which was close to that of Olaparib. The compounds I [R = 5-bromo-2-furyl] (IC50 = 43.56 卤 0.69渭M) and I [R = 5-chloro-2-furyl] (IC50 = 36.69 卤 0.83渭M) displayed good antiproliferation activity on MDA-MB-436 cells and inactivity on MCF-7 cells, indicating that they had high selectivity and targeting. The mol. docking method was used to explore the binding mode of compound I [R = 5-bromo-2-furyl] and PARP-1, and implied that the formation of hydrogen bond was essential for PARP-1 inhibition activities. This study also showed that in the hydrophobic pocket (AD binding sites), the introduction of strong electroneg. groups (furan ring, e.g.) or halogen atoms in the side chain of benzimidazole might improve its inhibitory activity and this strategy could be applied in further research. In the experiment, the researchers used many compounds, for example, 1H-Imidazole-4-carboxamide (cas: 26832-08-6Category: imidazoles-derivatives).
1H-Imidazole-4-carboxamide (cas: 26832-08-6) belongs to imidazole derivatives. Many natural products, especially alkaloids, contain the imidazole ring. These imidazoles share the 1,3-C3N2 ring but feature varied substituents. Imidazole also acts as a microtubule destabilizing agents and inhibits topoisomerase and Cytochrome P450 Family 26 Subfamily A Member 1 (CYP26A1) enzymes.Category: imidazoles-derivatives
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem