Spirooxindoles as Potential Pharmacophores.

OBJECTIVE: The spirooxindole heterocyclic scaffold is found in many natural products and has been identified as an important bioactive agent. BACKGROUND: Over the past few decades, various spirooxindole-containing compounds have been reported to possess biological properties and hence found in the structure of many synthetic pharmaceuticals. This mini-review describes the most promising examples of this class of compounds possessing biological activity including anticancer, anti-inflammatory, and antimicrobial activities. CONCLUSION: The current review focuses on the biological activity of compounds containing the spirooxindole scaffold.

Experimental and DFT Computational Insight into Nitrosamine Photochemistry-Oxygen Matters.

A nitrosamine photooxidation reaction is shown to generate a peroxy intermediate by experimental physical-organic methods. The irradiation of phenyl and methyl-substituted nitrosamines in the presence of isotopically labeled 18-oxygen revealed that an O atom was trapped from a peroxy intermediate to trimethylphosphite or triphenylphosphine, or by nitrosamine itself, forming two moles of nitramine. The unstable peroxy intermediate can be trapped at low temperature in postphotolyzed solution in the dark. Chemiluminescence was also observed upon thermal decomposition of the peroxy intermediate, that is, when a postphotolysis low-temperature solution is brought up to room temperature. A DFT study provides tentative information for cyclic nitrogen peroxide species on the reaction surface.

31 P NMR Evidence for Peroxide Intermediates in Lipid Emulsion Photooxidations: Phosphine Substituent Effects in Trapping.

Intralipid is a lipid emulsion used in photodynamic therapy (PDT) for its light scattering and tissue-simulating properties. The purpose of this study is to determine whether or not Intralipid undergoes photooxidation, and we have carried out an Intralipid peroxide trapping study using a series of phosphines [2'-dicyclohexylphosphino-2,6-dimethoxy-1,1'-biphenyl-3-sulfonate, 3-(diphenylphosphino)benzenesulfonate, triphenylphosphine-3,3',3''-trisulfonate and triphenylphosphine]. Our new findings are as follows: (1) An oxygen atom is transferred from Intralipid peroxide to the phosphine traps in the dark, after the photooxidation of Intralipid. 3-(Diphenylphosphino)benzenesulfonate is the most suitable trap in the series owing to a balance of nucleophilicity and water solubility. (2) Phosphine trapping and monitoring by 31 P NMR are effective in quantifying the peroxides in H2 O. An advantage of the technique is that peroxides are detected in H2 O; deuterated NMR solvents are not required. (3) The percent yield of the peroxides increased linearly with the increase in fluence from 45 to 180 J cm-2 based on our trapping experiments. (4) The photooxidation yields quantitated by the phosphines and 31 P NMR are supported by the direct 1 H NMR detection using deuterated NMR solvents. These data provide the first steps in the development of Intralipid peroxide quantitation after PDT using phosphine trapping and 31 P NMR spectroscopy.

Curcumin: Not So Spicy After All.

BACKGROUND: This is a short review on the most recent studies on curcumin and its analogs, including the studies from the laboratories of authors. The diverse medicinal properties of curcumin itself reported in the recent years are reviewed. Although curcumin has shown great potential in treating various diseases, it has not been approved as a clinical drug candidate because of its poor pharmacokinetics. METHOD: The recent methods developed to solve this problem are briefly described. CONCLUSION: The biological and other properties of synthetic curcumin analogs (diarylheptanoids and diarylpentanoid monocarbonyl derivatives) reported in the recent literature are also presented.

Convenient access to 5-arylisoindolo[2,1- α]quinolin-11(6a H)-ones.

Substituted isoindoloquinolinones were obtained from N-aryl-3-hydroxyisoindolinones and aryl alkynes under Lewis acid-catalyzed conditions in 30-99% yields.

Spiroindoles as Potential Pharmacophores.

The spiroindole heterocyclic scaffold is found in many natural products and has been identified as an important bioactive agent. Over the past few decades, various spiroindole-containing compounds have been reported to possess biological properties and hence found in the structure of many synthetic pharmaceuticals. This mini-review describes the most promising examples of this class of compounds possessing biological activity including anticancer, anti-inflammatory, and antimicrobial activities. To the best of our knowledge, the earlier reviews did not cover the pharmaceutical properties of synthetic and naturally occurring spiroindoles; thus, the current review focuses on the biological activity of compounds containing the spiroindole scaffold.

Synthesis and molecular modeling of antimicrobial active fluoroquinolone-pyrazine conjugates with amino acid linkers.

Novel fluoroquinolone-pyrazine conjugates 7a-h with amino acid linkers were synthesized in good yields utilizing benzotriazole chemistry. Antimicrobial bioassay showed that the synthesized bis-conjugates have antimicrobial properties comparable to the parent drugs. Compound 7h showed superior antibacterial activity against Staphylococcus aureus and Streptococcus pyogenes (MIC=74.6 µM and 149.3 µM, respectively). This matched well with the estimated values obtained from 3D-pharmacophore and 2D-QSAR studies (MIC=67 µM and 92.9 µM, respectively).

Synthesis of o-sulfamidotriazobenzenes from 1,1'-sulfonylbis(benzotriazole).

Easily accessible 1,1'-sulfonylbis(benzotriazole) (Bt2SO2, 1) reacts with secondary amines at room temperature to afford (i) the corresponding o-sulfamidotriazobenzenes 2a-d (53-75%) via concurrent substitution of the first and ring opening of the second benzotriazolyl group and (ii) N-sulfonylbenzotriazoles 3b,c,e,f (7-73%). 1-(Morpholine-4-sulfonyl)-1H-benzotriazole 3c reacts with piperidine, pyrolidine, and N-methylpiperazine under microwave irradiation (120 W) at 120 degrees C for 10 min to give the unsymmetrical sulfamides 4a-c (80-90%).

NMR spectra, GIAO and charge density calculations of five-membered aromatic heterocycles.

The B3LYP/6-31+G(d) molecular geometry optimized structures of 17 five-membered heterocycles were employed together with the gauge including atomic orbitals (GIAO) density functional theory (DFT) method at the B3LYP/6-31+G(d,p), B3LYP/6-311++G(d,p) and B3LYP/6-311+G(2d,p) levels of theory for the calculation of proton and carbon chemicals shifts and coupling constants. The method of geometry optimization for pyrrole (1), N-methylpyrrole (2) and thiophene (7) using the larger 6-311++G(d,p) basis sets at the B3LYP/6-31+G(d,p), B3LYP/6-311++G(d,p), B3LYP/6-31+G(2d,p) and B3LYP/cc-pVTZ levels of theory gave little difference between calculated and experimental values of coupling constants. In general, the (1)H and 13C chemical shifts for all compounds are in good agreement with theoretical calculations using the smaller 6-31 basis set. The values of nJHH(n=3, 4, 5) and rmnJ(CH)(n=1, 2, 3, 4) were predicted well using the larger 6-31+G(d,p) and 6-311++G(d,p) basis sets and at the B3LYP/6-31+G(d,p), B3LYP/6-311++G(d,p), B3LYP/6-31+G(2d,2p) levels of theory. The computed atomic charges [Mülliken; Natural Bond Orbital Analysis (NBO); Merz-Kollman (MK); CHELP and CHELPG] for the B3LYP/6-311++G(d,p) geometry optimized structures of 1-17 were used to explore correlations with the experimental proton and carbon chemical shifts.

1-Benzotriazol-1-yl-3,3,3-trifluoro-2-methoxy-2- phenylpropan-1-ones: Mosher-Bt reagents.

Benzotriazole derivatives of 3,3,3-trifluoro-2-methoxy-2-phenylpropionic acid react with water-soluble amino acids and peptides in an acetonitrile/water (2:1) mixture to give the corresponding amides in quantitative yield.

Alkyl, unsaturated, (hetero)aryl, and N-protected alpha-amino ketones by acylation of organometallic reagents.

Stable and easily accessible N-acylbenzotriazoles, derived from a variety of aliphatic, unsaturated, (hetero)aromatic, and N-protected alpha-amino carboxylic acids, were reacted with Grignard and heteroaryllithium reagents to afford corresponding ketones in good to excellent yields.

Nanoassembly of a fractal polymer: a molecular "Sierpinski hexagonal gasket".

Mathematics and art converge in the fractal forms that also abound in nature. We used molecular self-assembly to create a synthetic, nanometer-scale, Sierpinski hexagonal gasket. This nondendritic, perfectly self-similar fractal macromolecule is composed of bis-terpyridine building blocks that are bound together by coordination to 36 Ru and 6 Fe ions to form a nearly planar array of increasingly larger hexagons around a hollow center.

Benzotriazole-assisted thioacylation.

[Chemical reaction: See text] Benzotriazole reagents for thioacylation (RCSBt), thiocarbamoylation (RR'NCSBt), aryl/alkoxythioacylation (ROCSBt), and aryl/alkylthiothioacylation (RSCSBt) are synthesized, and their utility is assessed by syntheses of representative heteroaryl thioureas 3a-g, thioamides 15a-s, thionoesters 16a-h, thiocarbamates 17a-e, dithiocarbamates 18a-d, thiocarbonates 19a-c, and dithiocarbonates 20a-c.

Towards ordered architectures: self-assembly and stepwise procedures to the hexameric metallomacrocycles [arylbis(terpyridinyl)6FeII6-n-RuIIn] (n=0,2,3,5).

Hexameric metallomacrocycles are a new class of ordered rigid-macromolecules which possess unique structural, electronic, and physical characteristics. Directed- and self-assembly methods for the construction of these stable bis(terpyridine)-based materials are investigated by using both Fe(II) and Ru(II) as the coordinating metals. These heterometallomacrocycles and their homocounterparts are structurally compared, and their attendant electrochemical properties are analyzed and evaluated. These studies demonstrate the potential to create stable, nanoscale, doughnut-shaped, molecular assemblies with envisioned ramifications for energy storage and release, as well as nanoscale molecular electronic and magnetic devices.