Stacking-dependent tetracolour luminescence and mechanofluorochromic properties of an isoquinoline derivative with aggregation-induced emission

Although nearly one-third of organic compounds have polymorphism, more than three polymorphs with definite crystalline structures in an organic molecule are very rare. Herein, an aggregation-induced-emission-active isoquinoline derivative containing ethyl...

Antimalarial Properties of Isoquinoline Derivative from Streptomyces hygroscopicus subsp. Hygroscopicus: An In Silico Approach

Malaria is one of the life-threatening diseases in the world. The spread of resistance to antimalarial drugs is a major challenge, and resistance to artemisinin has been reported in the Southeast Asian region. In the previous study, the active compound of Streptomyces hygroscopicus subsp. Hygroscopicus (S. hygroscopicus), eponemycin, has been shown to have antimalarial effects. To further analyze the effects of other active compounds on the Plasmodium parasite, identifying and analyzing the effectiveness of compounds contained in S. hygroscopicus through instrumentation of liquid chromatography/mass spectrometry (LC/MS) and in silico studies were very useful. This study aimed at identifying other derivative compounds from S. hygroscopicus and screening the antimalarial activity of the compound by assessing the binding affinity, pharmacokinetic profile, and bond interaction. The derivative compounds were identified using LC/MS. Protein targets for derivative compounds were found through literature studies, and the results of identification of compounds and protein targets were reconstructed into three-dimensional models. Prediction of pharmacokinetic profiles was carried out using Swiss ADME. Screening of protein targets for the derivative compound was carried out using the reverse molecular docking method. Analyzing bond interaction was done by LigPlot. One compound from S. hygroscopicus, i.e., 6,7-dinitro-2-[1, 2, 4]triazole-4-yl-benzo[de]isoquinoline-1,3-dione, was successfully identified using LC/MS. This compound was an isoquinoline derivative compound. Through literature studies with inclusion criteria, thirteen protein targets were obtained for reverse molecular docking. This isoquinoline derivative had the potential to bind to each protein target. The pharmacokinetic profile showed that this compound had the drug-likeness criteria. Conclusion. 6,7-Dinitro-2-[1, 2, 4]triazole-4-yl-benzo[de]isoquinoline-1,3-dione has antimalarial activity as shown by reverse molecular docking studies and pharmacokinetic profiles. The best inhibitory ability of compounds based on bond affinity is with adenylosuccinate synthetase.

Structural characterization and crystal packing of the isoquinoline derivative

We report the crystal and molecular structure of a new isoquinoline-derivative, namely methyl O-[(11R, 11aS)-4-oxo-1, 3, 4, 6, 11, 11a-hexahydro-2H-pyrido[1, 2-b]isoquinolin-11-yl]carbonodithioate (I), C15H17NO2S2, which crystallizes in the non-centrosymmetric space group P212121 and its absolute structure was confirmed by anomalous dispersion effects in diffraction measurements on the crystals. Two central six-membered heterocyclic rings adopt a distorted half-chair conformation. The molecules are linked by a combination of weak C—H∙∙∙O, C—H∙∙∙S, C—H∙∙∙p inter- and intra-molecular interactions resulting in a three-dimensional network in the crystal structure. Crystal Data for C15H17NO2S2 (M =307.41 g/mol): orthorhombic, space group P212121 (no. 19), a = 5.2804(5) Å, b = 8.1347(17) Å, c = 35.015(4) Å, V = 1504.1(4) Å3, Z = 4, T = 298(2) K, μ(MoKα) = 0.354 mm-1, Dcalc =1.358 g/cm3, 20270 reflections measured (5.522° ≤ 2Θ ≤ 50.69°), 2757 unique (Rint = 0.0346, Rsigma = 0.0203) which were used in all calculations. The final R1 was 0.0389 (I > 2σ(I)) and wR2 was 0.0965 (all data).

Berberine Nanosuspension Enhances Hypoglycemic Efficacy on Streptozotocin Induced Diabetic C57BL/6 Mice

Berberine (Ber), an isoquinoline derivative alkaloid and active ingredient of Coptis, has been demonstrated to possess antidiabetic activities. However its low oral bioavailability restricts its clinical application. In this report, Ber nanosuspension (Ber-NS) composed of Ber and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was prepared by high pressure homogenization technique. Antidiabetic effects of Ber-NS relative to efficacy of bulk Ber were evaluated in streptozotocin (STZ) induced diabetic C57BL/6 mice. The particle size and zeta potential of Ber-NS were 73.1 ± 3.7 nm and 6.99 ± 0.17 mV, respectively. Ber-NS (50 mg/kg) treatment via oral gavage for 8 weeks resulted in a superior hypoglycemic and total cholesterol (TC) and body weight reduction effects compared to an equivalent dose of bulk Ber and metformin (Met, 300 mg/kg). These data indicate that a low dosage Ber-NS decreases blood glucose and improves lipid metabolism in type 2 diabetic C57BL/6 mice. These results suggest that the delivery of Ber as a nanosuspension is a promising approach for treating type 2 diabetes.

Crystal structures of 2-methoxyisoindoline-1,3-dione, 1,3-dioxoisoindolin-2-yl methyl carbonate and 1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-2-yl methyl carbonate: three anticonvulsant compounds

The title compounds, C9H7NO3, (1), C10H7NO5, (2), and C14H9NO5, (3), are three potentially anticonvulsant compounds. Compounds (1) and (2) are isoindoline derivatives and (3) is an isoquinoline derivative. Compounds (2) and (3) crystallize with two independent molecules (AandB) in their asymmetric units. In all three cases, the isoindoline and benzoisoquinoline moieties are planar [r.m.s. deviations are 0.021 Å for (1), 0.04 and 0.018 Å for (2), and 0.033 and 0.041 Å for (3)]. The substituents attached to the N atom are almost perpendicular to the mean planes of the heterocycles, with dihedral angles of 89.7 (3)° for the N—O—Cmethylgroup in (1), 71.01 (4) and 80.00 (4)° for the N—O—C(=O)O—Cmethylgroups in (2), and 75.62 (14) and 74.13 (4)° for the same groups in (3). In the crystal of (1), there are unusual intermolecular C=O...C contacts of 2.794 (1) and 2.873 (1) Å present in moleculesAandB, respectively. There are also C—H...O hydrogen bonds and π–π interactions [inter-centroid distance = 3.407 (3) Å] present, forming slabs lying parallel to (001). In the crystal of (2), theAandBmolecules are linked by C—H...O hydrogen bonds, forming slabs parallel to (10-1), which are in turn linkedviaa number of π–π interactions [the most significant centroid–centroid distances are 3.4202 (7) and 3.5445 (7) Å], forming a three-dimensional structure. In the crystal of (3), theAandBmolecules are linkedviaC—H...O hydrogen bonds, forming a three-dimensional structure, which is consolidated by π–π interactions [the most significant inter-centroid distances are 3.575 (3) and 3.578 (3) Å].

A Novel Route to Isoquinoline[2,1-g][1,6]naphthyridine, Pyrazolo[5,1-a] isoquinoline and Pyridazino[4´,5´:3,4]pyrazolo[5,1-a]isoquinoline Derivatives With Evaluation of Antitumor Activities

(E)-2-Chloro-3-(2-cyanovinyl)-9,10-dimethoxy-4-oxo-6,7-dihydro-4H-pyrido[2,1-a] isoquinoline- 1-carbonitrile (5) was obtained by treatment of the 2-chloro-3-formylpyrido[2,1-a]isoquinoline derivative 3 with 2-(triphenylphosphoranylidene)acetonitrile (4). Treatment of 5 with sodium azide afforded the corresponding azido compound 6 which could be reduced by sodium dithionite to compound 7. A novel isoquinolino[2,1-g][1,6]naphthyridine derivative 11 was obtained by the reaction of phenyl isothiocyanate with the phosphorane compound 8, which was prepared by the reaction of compound 6 with triphenylphosphine. Treatment of 5 with amines 12a-c and thiophenols 14a-c in refluxing ethanol afforded the corresponding substitution products 13a-c and 15a-c, respectively. Also, the reaction of 1 with a-oxo hydroxamoyl chlorides 16 was reinvestigated, and the synthesized pyrazoloisoquinolines 19a-f and pyridazinopyrazoloisoquinolines 20a, e were screened for their in vitro antitumor activities.