In the title compound, C25H19NO4, the indole moiety is not completely planar, the heterocyclic ring being distorted very slightly towards a half-chair conformation. The benzoyl and 4-methoxyphenyl substituents are individually almost planar and are in a bisecting and nearly perpendicular configuration, respectively, with respect to the plane of the indole moiety. The molecular and packing structures in the crystal are stabilized by intramolecular and intermolecular C-H...O interactions.
In the syn- and anticlinal isomers of the title compound, C(22)H(18)N(2)O(6), the indole moiety is not completely planar, with the pyrrolidine ring being distorted very slightly towards a conformation intermediate between half-chair and envelope. The molecular and packing structures in the crystals of these isomers are stabilized by C-H...O interactions.
The crystal of the title compound, C(20)H(17)NO(4), which was used for collecting intensity data was twinned. Each of the two crystallographically independent molecules in the asymmetric unit has a planar indole moiety perpendicular to a planar oxopropyl moiety. The distribution of the bonds at the central C atom joining the oxopropyl, phenyl and indole substituents is also planar. The packing is stabilized by intermolecular C-H* * *O interactions, as well as by dipole-dipole and van der Waals interactions.
In the title compounds, C(21)H(18)N(2)O(4) and C(25)H(18)N(2)O(4), respectively, the five-membered ring of the indole system is almost planar. The oxetane and oxazole rings are individually planar. The orientations of the indole, oxetane, oxazole and phenyl moieties are conditioned by the sp(3) nature of the spiro-C atoms. In both compounds, the relative orientation of the indole and oxazole rings is opposite.
In the title compound, C(18)H(13)BrClNO(3), the heterocyclic ring of the indole is distorted from planarity towards an envelope conformation. The orientations of the indole, oxetane, chloro and bromophenyl substituents are conditioned by the sp(3) states of the spiro-junction and the Cl-attached C atoms.
In the title compound, C20H16N2O5, both of the 1-acetylisatin (1-acetyl-1H-indole-2,3-dione) moieties are planar and form a dihedral angle of 74.1 (1) degrees. Weak intermolecular hydrogen bonds and C-H...pi interactions stabilize the packing in the crystal.
Four tetracyclic oxindole alkaloids, 7(R)- and 7(S)-geissoschizol oxindole (1 and 2), 7(R),16(R)- and 7(S),16(R)-19(E)-isositsirikine oxindole (3 and 4), in addition to a taberpsychine derivative, N(4)-demethyltaberpsychine (5), were isolated from the Malayan Tabernaemontana corymbosa and the structures were established using NMR and MS analysis.
A series of hitherto unreported anthracene-embedded dispirooxindoles has been synthesized via a one-pot three-component 1,3-dipolar cycloaddition reaction of an azomethine ylide, generated in situ from the reaction of isatin and sarcosine to 10-benzylideneanthracen-9(10H)-one as a dipolarophile in 1-butyl-3-methylimidazolium bromide([bmim]Br), an ionic liquid. This reaction proceeded regio- and diastereoselectively, in good to excellent yields.
As a hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, Fluvastatin (FLV) is used for reducing low-density lipoprotein (LDL) cholesterol as well as to prevent cardiovascular problems. FLV showed cell line cytotoxicity and antitumor effect. Melittin (MEL) exhibits antineoplastic activity and is known to be promising as a therapeutic option for cancer patients. The aim of this work was to investigate the combination of FLV with MEL loaded hybrid formula of phospholipid (PL) with alpha lipoic acid (ALA) nanoparticles to maximize anticancer tendencies. This study examines the optimization of the prepared formulation in order to minimize nanoparticles size and maximize zeta potential to potentiate cytotoxic potentialities in colon cancer cells (Caco2), cell viability, cell cycle analysis and annexin V were tested. In addition to biological markers as P53, Bax, bcl2 and Caspase 3 evaluation The combination involving FLV PL ALA MEL showed enhanced cytotoxic potentiality (IC50 = 9.242 ± 0.35 µg/mL), about twofold lower, compared to the raw FLV (IC50 = 21.74 ± 0.82 µg/mL). According to studies analyzing cell cycle, optimized FLV PL ALA MEL was found to inhibit Caco2 colon cancer cells more significantly than other therapeutic treatments, wherein a higher number of cells were found to accumulate over G2/M and pre-G1 phases, whereas G0/G1/S phases witnessed the accumulation of a lower number of cells. The optimized formulation may pave the way for a novel and more efficacious treatment for colon cancer.
Matched MeSH terms: Indoles/pharmacology; Indoles/therapeutic use
Two independent molecules that differ in terms of rotation about the central S-N bond comprise the asymmetric unit of the title compound 1. The molecules have a V-shape with the dihedral angles between the fused ring system and benzene ring being 79.08(6)° and 72.83(5)°, respectively. The packing is mostly driven by p···p interactions occurring between the tolyl ring of one molecule and the C6 ring of the indole fused ring system of the other. DFT and IRC calculations for these and related 1-(arylsulfonyl)indole molecules showed that the rotational barrier about the S-N bond between conformers is within the 2.5-5.5 kcal/mol range. Crystal data for C16H13NO3S (1): Mr = 299.33, space group Pna21, a = 19.6152(4) Å, b = 11.2736(4) Å, c = 12.6334(3) Å, V = 2793.67(13) Å3, Z = 8, Z' = 2, R = 0.034.
A new series of triazinoindole analogs 1-11 were synthesized, characterized by EI-MS and (1)H NMR, evaluated for α-glucosidase inhibitory potential. All eleven (11) analogs showed different range of α-glucosidase inhibitory potential with IC50 value ranging between 2.46±0.008 and 312.79±0.06 μM when compared with the standard acarbose (IC50, 38.25±0.12 μM). Among the series, compounds 1, 3, 4, 5, 7, 8, and 11 showed excellent inhibitory potential with IC50 values 2.46±0.008, 37.78±0.05, 28.91±0.0, 38.12±0.04, 37.43±0.03, 36.89±0.06 and 37.11±0.05 μM respectively. All other compounds also showed good enzyme inhibition. The binding modes of these analogs were confirmed through molecular docking.
Many a times, community targeted strategy works in silo and done haphazardly without any long-term planning and impact to the community. This wayward fashion has cost us millions of dollars, lost resources and dimmed motiva-tion. Most of the time, incoherent planning and short-term targets are the motivators. Getting plans into policy is not a task to be taken lightly. Policies that are incoherent, disintegrated with organisational and national plans, will not be taken up as policy papers. Overcoming resistance is another method to ensure smoothness of policy acceptance. This involves enlisting communication with multiple stakeholders and hearing out qualms by community members. Community based insurance is an example. The initial social insurance has been in the agenda for multiple years already. In the past 3 years, this agenda has been sped up by political masterminds and NGOs. The Peka B40 and MySalam have been introduced in the Malaysian healthcare system. It is hoped that these two social health insurance will provide the much needed relief for community in the lower categories.
Photoelectrochemical oxidation of thiols was enhanced with a threshold potential of -0.35 V vs. Ag/AgCl by the use of a ZnPc/PCBM:P3HT/ZnO electode, which was prepared by removing the PEDOT:PSS/Au electrode of an inverted OPV device and coating it with ZnPc. A co-photocatalysis property of ZnPc was observed in the photoelectrochemistry and scanning Kelvin probe microscopy.
The title compound, C23H22FN5S, exists in a trans conformation with respect to the methene C=C and the acyclic N=C bonds. The 1,2,4-triazole-5(4H)-thione ring makes dihedral angles of 88.66 (9) and 84.51 (10)°, respectively, with the indole and benzene rings. In the crystal, mol-ecules are linked by pairs of N-H⋯S hydrogen bonds, forming inversion dimers with an R 2 (2)(8) ring motif. The dimers are linked via C-H⋯π inter-actions, forming chains along [1-10]. The chains are linked via π-π inter-actions involving inversion-related triazole rings [centroid-centroid distance = 3.4340 (13) Å], forming layers parallel to the ab plane.
In the title compound, C26H22N2O2, the dihedral angles between the 1-methyl-indole units (A and B) and the benzoic acid moiety (C) are A/B = 64.87 (7), A/C = 80.92 (8) and B/C = 75.05 (8)°. An intra-molecular C-H⋯O inter-action arising from the methyne group helps to establish the conformation. In the crystal, R22(8) carb-oxy-lic acid inversion dimers linked by pairs of O-H⋯O hydrogen bonds are observed. A Hirshfeld surface analysis shows that the greatest contributions are from H⋯H, C⋯H/H⋯C and O⋯H/H⋯O contacts (percentage values = 54.6%, 29.6% and 10.1%, respectively).
Four new bisindoles of the vobasine-iboga type, conodiparines A-D were obtained from Tabernaemontana corymbosa which showed appreciable activity in reversing resistance in vincristine-resistant KB cells.
Bisindole analogs 1-17 were synthesized and evaluated for their in vitro β-glucuronidase inhibitory potential. Out of seventeen compounds, the analog 1 (IC50=1.62±0.04 μM), 6 (IC50=1.86±0.05 μM), 10 (IC50=2.80±0.29 μM), 9 (IC50=3.10±0.28 μM), 14 (IC50=4.30±0.08 μM), 2 (IC50=18.40±0.09 μM), 19 (IC50=19.90±1.05 μM), 4 (IC50=20.90±0.62 μM), 7 (IC50=21.50±0.77 μM), and 3 (IC50=22.30±0.02 μM) showed superior β-glucuronidase inhibitory activity than the standard (d-saccharic acid 1,4-lactone, IC50=48.40±1.25 μM). In addition, molecular docking studies were performed to investigate the binding interactions of bisindole derivatives with the enzyme. This study has identified a new class of potent β-glucouronidase inhibitors.
Conformational search for the most stable geometry connection of 16 sets of polydopamine (PDA) tetramer subunits has been systematically investigated using density functional theory (DFT) calculations. Our results indicated that the more planar subunits are, the more stable they are. This finding is in good agreement with recent experimental observations, which have suggested that PDA are composed of the nearly planar subunits that appear to be stacked together via the π-π interactions to form graphite-like layered aggregates associated with the balance of the intramolecular hydrogen bonds and steric effects from the indole and catechol moieties. Molecular dynamics (MD) simulations of 16 spherical clusters of the tetramer subunits of PDA in the gas and aqueous phase were performed at 298 K and confirmed the stability of supramolecular tetramer aggregates. The complex formation and binding energy of all 16 clusters are very strong although the shapes of the clusters in aqueous solution are not spherical and are very much different from those in the gas phase. The aggregations of all 16 clusters in aqueous solution were also confirmed from the profiles of the Kratky plot and the radius of gyration of all clusters. Our MD results in both gas phase and aqueous solution pointed out that there are high possibilities of aggregations of the 16 kinds of tetramer subunits although the conformations of each tetramer subunit are not flat. In summary, this work brings an insight into the controversial structure of PDA tetramer units and explains some of the important structural features found in the aqueous phase in comparison to the gas phase.
Binding studies between a multi-targeted anticancer drug, sunitinib (SU) and human serum albumin (HSA) were made using fluorescence, UV-vis absorption, circular dichroism (CD) and molecular docking analysis. Both fluorescence quenching data and UV-vis absorption results suggested formation of SU-HSA complex. Moderate binding affinity between SU and HSA was evident from the value of the binding constant (3.04×104M-1), obtained at 298K. Involvement of hydrophobic interactions and hydrogen bonds as the leading intermolecular forces in the formation of SU-HSA complex was predicted from the thermodynamic data of the binding reaction. These results were in good agreement with the molecular docking analysis. Microenvironmental perturbations around Tyr and Trp residues as well as secondary and tertiary structural changes in HSA upon SU binding were evident from the three-dimensional fluorescence and circular dichroism results. SU binding to HSA also improved the thermal stability of the protein. Competitive displacement results and molecular docking analysis revealed the binding locus of SU to HSA in subdomain IIA (Sudlow's site I). The influence of a few common ions on the binding constant of SU-HSA complex was also noticed.
Twenty five derivatives of indole carbohydrazide (1-25) had been synthesized. These compounds were characterized using 1H NMR and EI-MS, and further evaluated for their α-amylase inhibitory potential. The analogs (1-25) showed varying degree of α-amylase inhibitory potential. ranging between 9.28 and 599.0µM when compared with standard acarbose having IC50 value 8.78±0.16µM. Six analogs, 25 (IC50=9.28±0.153µM), 22 (IC50=9.79±0.43µM), 4 (IC50=11.08±0.357µM), 1 (IC50=12.65±0.169µM), 8 (IC50=21.37±0.07µM) and 14 (IC50=43.21±0.14µM) showed potent α-amylase inhibition as compared to the standard acarbose (IC50=8.78±0.16µM). All other analogs displayed good to moderate inhibitory potential. Structure-activity relationship was established through the interaction of the active compounds with enzyme active site with the help of docking studies.