The Significance of Lipoproteins in the Development of Obesity.

Disruption of lipoprotein metabolism plays an important role in the development of several cardiovascular, inflammatory, and metabolic diseases. This review examines the importance of different types of lipoproteins and the role they play in the development of dyslipidemia in obesity. The causes and consequences associated with the disruption of lipid metabolism and its significance in the pathogenesis of obesity are considered. The relationship between such pathological processes, which occur alongside obesity as dyslipidemia and inflammation, is determined. In view of the current efficacy and toxicity limitations of currently approved drugs, natural compounds as potential therapeutic agents in the treatment of obesity are considered in the review. The complex mechanisms of lipid metabolism normalization in obesity found for these compounds can serve as one of the confirmations of their potential efficacy in treating obesity. Nanoparticles can serve as carriers for the considered drugs, which can improve their pharmacokinetic properties.

Simple entry into N-tert-butyl-iminophosphonamide rare-earth metal alkyl and chlorido complexes.

In situ protolysis reaction of a highly basic and sterically hindered N,N'-di-tert-butyl-iminophosphonamide ligand Ph2P([double bond, length as m-dash]N-tBu)(NH-tBu) = (NPN(tBu))H (1) with equimolar or hemimolar amounts of rare-earth metal tris-alkyls leads to dialkyl [(NPN(tBu))Ln(CH2SiMe3)2(THF)n] (Ln = Sc, n = 0 (2), Ln = Y, n = 1 (3)) and monoalkyl species [(NPN(tBu))2Ln(CH2SiMe3)] (Ln = Y (4), Nd (6), Sm (7)). One-pot reaction of [ScCl3(THF)3]/1/MeLi in 1/2/3 eq. ratio gives [(NPN(tBu))2Sc(THF)CH3] 5. Further reaction of 4 with phenylacetylene resulted in the formation of the Y-alkynyl complex [(NPN(tBu))2Y(-C[triple bond, length as m-dash]CPh)] 8. Alkyl abstraction in 2, 3 and 4 by reaction with [PhNMe2H](+)[B(C6F5)4](-) resulted in the formation of cationic alkyl complex ion-pairs [(NPN(tBu))Ln(CH2SiMe3)(THF)n](+)[B(C6F5)4](-) (Ln = Sc (9), Y (10)) and [(NPN(tBu))2Y(THF)n](+)[B(C6F5)4](-)11, as confirmed by NMR data. The reaction of bis-NPN alkyl complexes with CHCl3 is the simplest and most reliable protocol to synthesize bis-NPN-chlorido complexes [(NPN(tBu))2Ln-Cl] (Ln = Sc (12), Y (13), Nd (14), Sm (15), Gd (16), Tb (17), Yb (18) and Lu (19)), which can become new post-metallocene alternatives to the prominent organolanthanide building blocks [Cp*2LnX]. Partial hydrolysis of 12 leads to the formation of the oxido/chlorido-capped trinuclear complex [{(NPN(tBu))Sc(µ2-Cl)}3(µ3-O)(µ3-Cl)] 20. Molecular structures of 4, 6, 7, 13, 19 and 20 were confirmed by X-ray structure analyses.

Sulfinylamine metathesis at oxo metal species--convenient entry into imido metal chemistry.

The exchange of terminal metal oxo functionalities by N-organo and N-sulfonylimido functionalities via metathesis with bent, thus very reactive sulfinyl amines R-NSO and sulfinyl sulfonylamides R-SO(2)-NSO is described. It is demonstrated that in many cases sulfinyl amine metathesis offers a more convenient entry into imido complex synthesis than the much better investigated isocyanate metathesis at oxo complexes or condensation reactions with amines and silylated amines. Improved syntheses for some known key compounds and several new complexes of the type [V(NR)Cl(3)] and [M(NR)(2)Cl(2)] (M = Cr, Mo, W) are described. Emphasis is put on the synthesis of formerly unknown base free Lewis acids with electron-withdrawing N-substituents such as haloaryl and sulfonylaryl. Surprisingly, even [CrO(2)Cl(2)] is selectively transformed by sulfinylamines into aryl imido derivatives without any reduction by sulfur dioxide. The molecular structures of novel haloaryl imido complexes [Cr(NAr)(2)Cl(2)] Ar = C(6)F(5) and 2,4,6-Cl(3)C(6)H(2) as determined by X-ray crystallography are reported.

Dihydro-resveratrol--a potent dietary polyphenol.

Dihydro-resveratrol (dihydro-R), a prominent polyphenol component of red wine, has a profound proliferative effect on hormone-sensitive tumor cell lines such as breast cancer cell line MCF7. We found a significant increase in MCF7 tumor cells growth rates in the presence of picomolar concentrations of this compound. The proliferative effect of dihydro-R was not observed in cell lines that do not express hormone receptors (MDA-MB-231, BT-474, and К-562).

Discovery and SAR exploration of N-aryl-N-(3-aryl-1,2,4-oxadiazol-5-yl)amines as potential therapeutic agents for prostate cancer.

A new chemical series of antiproliferative compounds was identified via high-throughput screening on DU-145 human prostate carcinoma cell line (hit compound potency - 5.7 microM). Exploration of the two peripheral diversity vectors of the hit molecule in a hit-targeted library and testing of the resulting compounds led to SAR generalizations and identification of the 'best' pharmacophoric moieties. The latter were merged in a single compound that exhibited a 200-fold better potency than the original hit compound. Specific cancer cell cytotoxicity was confirmed for the most potent compounds.

P-Amino-cyclopentadienylidene-phosphoranes versus P-cyclopentadienyl-iminophosphoranes--tautomeric protic forms of a new bidentate CpPN ligand system.

The Staudinger reaction of cyclopentadienyl-phosphanes C5H5-PMe2 (P1), C5H5-PPh2 (P2), and C5Me4H-PMe2 (P3) with azides Me3SiN3, 1-AdN3 (Ad = 1-adamantyl) and DipN3 (Dip = 2,6-diisopropylphenyl) has been studied. The nature of the products depends on the substituents at the C5 ring, at the phosphorus and nitrogen atoms: A series of new P-amino-cyclopentadienylidene-phosphoranes 2-6 was synthesized by reactions of P1-P3 with 1-AdN3 (2-4) and DipN3 (5,6). In contrast, P-cyclopentadienyl-iminophosphoranes 1 and 7 were obtained as predominant tautomers by reaction of less CH-acidic P3 with less N-basic Me3SiN3 and DipN3. Both tautomers are protonated forms of ambident, potentially chelating constrained-geometry ligands. The molecular structures of three members of this "CpPN" ligand family, 3, 4 and 6, are characterized by X-ray crystallography.

Dichloro(1,2-dimethoxyethane)bis(tosylimido)molybdenum(VI), a versatile nitrene transfer reagent.

In the title compound, [Mo(C7H7NO2S)2Cl2(C4H10O2)], the Mo-Cl bond lengths are 2.3730 (8) and 2.3842 (8) A, the former being the shortest within the series of analogous structurally characterized bis(imido) Mo complexes. This fact clearly explains the very strong Lewis acidity of the metal centre in this complex and, as a result, its synthetic versatility as a nitrene transfer reagent towards different phosphanes and strained cycloolefins.

First transition-metal complexes of S=P(NHBu t)3.

The first transition-metal (Rh(I), Mo(VI), Ni(II)) complexes of S[double bond, length as m-dash]P(NHBu(t))(3) have been synthesized via metathetical reactions of mono-lithiated and [Rh(CO)(2)Cl](2), (Bu(t)N)(2)MoCl(2)(dme) and NiBr(2)(dme). Surprisingly in the molecular structure of the Ni(II)-complex both hard-soft (N,S) and hard-hard (N,N[prime or minute]) chelation modes of are realized.