40101-59-5Relevant articles and documents
New cyanopyridine-based scaffold as PIM-1 inhibitors and apoptotic inducers: Synthesis and SARs study
Farrag, Amel M.,Ibrahim, Mona H.,Mehany, Ahmed B.M.,Ismail, Magda M.F.
, (2020)
Two novel series of 6-(4-benzamido-/4-phthalimido)-3-cyanopyridine derivatives were designed and synthesized as inhibitors of PIM-1 kinase. Based on cytotoxicity results via MTT assay against prostate carcinoma PC3, human hepatocellular carcinoma HepG2 and breast adenocarcinoma MCF-7 cell lines, the most potent cytotoxic cyanopyridine hits, 6, 7, 8, 12 and 13 were 1.5–3.3 times more inhibitor of cell proliferation than the reference standard, 5-FU. Selectivity profile of the latter compounds on normal human cells (WI-38), was executed, indicating that they are highly selective (IC50 > 145 μM) in their cytotoxic effect. The promising compounds were further evaluated as PIM-1 kinase inhibitors. These compounds elicited remarkable inhibition of PIM-1 kinase (76.43–53.33%). Extensive studies on apoptosis were conducted for these compounds; they enhanced caspase-3 and boosted the Bax/Bcl-2 ratio 27-folds in comparison to the control. Molecular docking study of the most potent compound, 13 in PIM-1 kinase active site was consistent with the in vitro activity. Finally, prediction of chemo-informatic properties released compound 13 as the most promising ligand.
Visible-Light-Induced Metal-/Photocatalyst-Free C-H Bond Imidation of Arenes
Kuribara, Takahito,Nakajima, Masaya,Nemoto, Tetsuhiro
supporting information, p. 2235 - 2239 (2020/03/13)
In this study, a visible-light-induced intermolecular C-H bond imidation of arenes was achieved at ambient condition. By using simple phthalimide with (diacetoxyiodo)benzene and molecular iodine, direct metal-/photocatalyst-free C-N bond formation was achieved. The imidation protocol was designed by using time-dependent density functional theory calculations and experimentally demonstrated for 28 substrates with as high as 96% yield. Mechanistic studies indicated that radical-mediated aromatic substitution occurred via photolysis of N-iodophthalimide under visible-light irradiation.
Synthesis and Evaluation of Novel Isoindoline-1,3-dione Derivatives as Anticancer Agents
Radwan,Alminderej,Premanathan,Alwashmi,Alhumaydhi,Alturaiki,Alsagaby
, p. 1087 - 1098 (2020/12/30)
Abstract: N-Substituted imides, isoindoline-1,3-dione derivatives, were synthesized, characterized, and investigated against blood cancer using K562 and Raji cell lines. Cytotoxicity assay was performed to determine the influence of phthalimide derivatives on the survival of the cancer cells. In addition, flow-cytometry with annexin-V-conjugated with fluorescein isothiocyanate (FITC) and propidium iodide (PI) stains were used to investigate the type of cell death induced by our phthalimide derivatives. 2-(4-(2-Bromoacetyl)phenyl)isoindoline-1,3-dione showed the most inhibitory effect on the viability of the cancer cells (CC50 = 0.26 μg/mL for Raji cells and 3.81 μg/mL for K562 cells). As a result, 2-(4-(2-bromoacetyl)phenyl)isoindoline-1,3-dione was selected for further investigations to determine the type of cellular death against Raji cells. The analysis found that this compound induced apoptosis and necrosis in Raji cells. Our findings provide a basis for a further study to investigate the impact of additional alkylating imides on the survival of blood cancer cells, particularly against Raji cells.
