Search Results (4)

Novel analogs of quinoline and isoindoline containing various heterocycles, such as tetrazole, triazole, pyrazole, and pyridine, were synthesized and characterized using FT-IR, NMR, and mass spectroscopy, and their antioxidant and antidiabetic activities were investigated. The previously synthesized compound 1 was utilized in conjugation with ketone-bearing tetrazole and isoindoline-1,3-dione to synthesize Schiff’s bases 2 and 3. Furthermore, hydrazide 1 was treated with aryledines to provide pyrazoles 4a–c. Compound 5 was obtained by treating 1 with potassium thiocyanate, which was then cyclized in a basic solution to afford triazole 6. On the other hand, pyridine derivatives 7a–d and 8a–d were synthesized using 2-(4-acetylphenyl)isoindoline-1,3-dione via a one-pot condensation reaction with aryl aldehydes and active methylene compounds. From the antioxidant and antidiabetic studies, compound 7d showed significant antioxidant activity with an EC₅₀ = 0.65, 0.52, and 0.93 mM in the free radical scavenging assays (DPPH, ABTS, and superoxide anion radicals). It also displayed noteworthy inhibitory activity against both enzymes α-glycosidase (IC₅₀: 0.07 mM) and α-amylase (0.21 mM) compared to acarbose (0.09 mM α-glycosidase and 0.25 mM for α-amylase), and higher than in the other compounds. During in silico assays, compound 7d exhibited favorable binding affinities towards both α-glycosidase (−10.9 kcal/mol) and α-amylase (−9.0 kcal/mol) compared to acarbose (−8.6 kcal/mol for α-glycosidase and −6.0 kcal/mol for α-amylase). The stability of 7d was demonstrated by molecular dynamics simulations and estimations of the binding free energy throughout the simulation session (100 ns). Full article

A series of divalent manganese complexes [M^II(HL^1–6)Cl₂] with the 1,3-bis(2’-Ar-imino)isoindolines (HLⁿ, n = 1–6, Ar = pyridyl, 4-methylpyridyl, imidazolyl, thiazolyl, benzimidazolyl and N-methylbenzimidazolyl, respectively) including the previously reported ligands (HL^{1–2, 4–6}) and complexes ([M^II(HL^1,5)Cl₂]) have been prepared and characterized by electrochemical and spectroscopic methods. In these complexes, it was possible to control the redox potential of the metal center by varying the aryl substituent on the bis-iminoisoindoline moiety, and investigate its effect in a catalase-like reaction, and oxidative bleaching process in buffered aqueous solution. The kinetics of the dismutation of H₂O₂ into H₂O and O₂, and the oxidative degradation of morin by H₂O₂ were investigated in buffered water, where the reactivity of the catalysts in both systems was markedly influenced by the redox and Lewis acidic properties of the metal centers and the concentration of the bicarbonate ions. Both the catalase-like and bleaching activity of the catalysts showed a linear correlation with the Mn^III/Mn^II redox potentials. The E_1/2 spans a 561 mV range from 388 mV (Ar = benzymidazolyl) to 948 mV (Ar = 4-methylpyridyl) vs. the SCE. The amount of bicarbonate is a critical issue for the in situ formation of peroxycarbonate as a versatile oxidant, and its participation in the formation of high valent Mn^IV = O species. Full article

Pyrrolocarbazoles are important structural motives present in many natural products and pharmaceuticals. Particularly, pyrrolo [3,4-a] carbazole-1,3-diones have attracted much attention as analogues of bioactive compounds, such as anticancer agent granulatimide. Surprisingly, only a few methods for the synthesis of these compounds have been reported in the literature, and they are almost limited to the Diel–Alder cycloaddition of 3-vinylindoles. We have recently developed a multicomponent synthesis of polysubstituted anilines starting from ,-unsaturated carbonyls, isocyanides and dienophiles. Here we report the application of this tandem [4 + 1]–[4 + 2] cycloaddition procedure for the synthesis of 4-amino-5-arylisoindoline-1,3-diones, which are then cyclized by means of a metal catalyzed intramolecular C-N coupling, affording structurally diverse, natural product-like pyrrolo [3,4-a] carbazole-1,3-diones with high yields and selectivities. Full article

Enterovirus 71 (EV-A71) is the main causative pathogen of childhood hand, foot and mouth disease. Effective medicine is currently unavailable for the treatment of this viral disease. Using the fragment-hopping strategy, a series of 2-aryl-isoindolin-1-one compounds were designed, synthesized and investigated for their in vitro antiviral activity towards multiple EV-A71 clinical isolates (H, BrCr, Shenzhen98, Jiangsu52) in Vero cell culture in this study. The structure–activity relationship (SAR) studies identified 2-phenyl-isoindolin-1-ones as a new potent chemotype with potent antiviral activity against EV-A71. Ten out of the 24 tested compounds showed significant antiviral activity (EC₅₀ < 10 µM) towards four EV-A71 strains. Compounds A3 and A4 exhibited broad and potent antiviral activity with the 50% effective concentration (EC₅₀) values in the range of 1.23–1.76 μM. Moreover, the selectivity indices of A3 and A4 were significantly higher than those of the reference compound, pirodavir. The western blotting experiment indicated that the viral VP1 was significantly decreased at both the protein and RNA level in a dose-dependent manner following treatment with compound A3. Moreover, compound A3 inhibited the viral replication by acting on the virus entry stage. In summary, this study led to the discovery of 2-aryl-isoindolin-1-ones as a promising scaffold with potent anti-EV-A71 activities, which deserves further in-depth studies. Full article