Rational Design, Synthesis and Binding Affinity Studies of Anthraquinone Derivatives Conjugated to Gonadotropin-Releasing Hormone (GnRH) Analogues towards Selective Immunosuppression of Hormone-Dependent Cancer.

Gonadotropin-releasing hormone (GnRH) is pivotal in regulating human reproduction and fertility through its specific receptors. Among these, gonadotropin-releasing hormone receptor type I (GnRHR I), which is a member of the G-protein-coupled receptor family, is expressed on the surface of both healthy and malignant cells. Its presence in cancer cells has positioned this receptor as a primary target for the development of novel anti-cancer agents.

Monitoring of Volatile Organic Compounds in Strawberry Genotypes over the Harvest Period.

Volatile Organic Compounds (VOCs) over the harvest period have been assessed in twenty-five strawberry genotypes cultivated in western Greece. Using liquid-liquid extraction and gas chromatography-mass spectrometry (GC--MS), twenty-eight volatiles were monitored at early (T1) and mid-harvest (T3) time points to investigate the effect of the genotype and harvest time on strawberry volatilome. A quantitative impact of both harvest date and genotype on VOCs associated with aroma was demonstrated, with the most significant VOCs being terpenes, esters, and acids, followed by lactones and furanones.

99mTc-DTPA Diuretic Renography with 3 hours late output fraction in the evaluation of hydronephrosis in children.

Objective: Dynamic renal scintigraphy complemented by late gravity assisted postvoid images to 60 minutes is a frequently used diagnostic test in the evaluation of hydronephrosis. The objective of this study is to evaluate the effectiveness in acquiring images at 180 minutes to calculate the late output fraction (LOF) of 99mTc-DTPA in the diagnosis of ureteropelvic junction obstruction (UPJO).

Materials And Methods: A retrospective study of 177 patients (196 renal units) of suspected cases of clinical UPJO was conducted.

Design, synthesis and evaluation of an anthraquinone derivative conjugated to myelin basic protein immunodominant (MBP) epitope: Towards selective immunosuppression.

Anthraquinone type compounds, especially di-substituted amino alkylamino anthraquinones have been widely studied as immunosuppressants. The anthraquinone ring is part of mitoxandrone that has been used for the treatment of multiple sclerosis (MS) and several types of tumors. A desired approach for the treatment of MS would be the immunosuppression and elimination of specific T cells that are responsible for the induction of the disease.

Biologically relevant conformational features of linear and cyclic proteolipid protein (PLP) peptide analogues obtained by high-resolution nuclear magnetic resonance and molecular dynamics.

Proteolipid protein (PLP) is one of the main proteins of myelin sheath that are destroyed during the progress of multiple sclerosis (MS). The immunodominant PLP epitope is known to induce experimental autoimmune encephalomyelitis (EAE, animal model of MS), wherein residues 144 and 147 are recognized by T cell receptor (TCR) during the formation of trimolecular complex with peptide-antigen and major histocompability complex. The conformational behavior of linear and cyclic peptide analogues of PLP, namely PLP and cyclic (139-151) (L, R) PLP have been studied in solution by means of nuclear magnetic resonance (NMR) methods in combination with unrestrained molecular dynamics simulations.

Design and Synthesis of Non-Peptide Mimetics Mapping the Immunodominant Myelin Basic Protein (MBP) Epitope to Function as T-Cell Receptor Antagonists.

Encephalitogenic T cells are heavily implicated in the pathogenesis of multiple sclerosis (MS), an autoimmune demyelinating disease of the central nervous system. Their stimulation is triggered by the formation of a trimolecular complex between the human leukocyte antigen (HLA), an immunodominant myelin basic protein (MBP) epitope, and the T cell receptor (TCR). We detail herein our studies directed towards the rational design and synthesis of non-peptide mimetic molecules, based on the immunodominant MBP epitope that is recognized by the TCR in complex with HLA.

Molecular dynamics at the receptor level of immunodominant myelin oligodendrocyte glycoprotein 35-55 epitope implicated in multiple sclerosis.

Multiple Sclerosis (MS) is a common autoimmune disease whereby myelin is destroyed by the immune system. The disease is triggered by the stimulation of encephalitogenic T-cells via the formation of a trimolecular complex between the Human Leukocyte Antigen (HLA), an immunodominant epitope of myelin proteins and T-cell Receptor (TCR). Myelin Oligodendrocyte Glycoprotein (MOG) is located on the external surface of myelin and has been implicated in MS induction.

Sulfinyl-Mediated Stereoselective Overman Rearrangements and Diels-Alder Cycloadditions.

Sulfinyl trichloroacetamides are readily obtained in excellent yields through a highly stereoselective Overman rearrangement. Related bis-allylic substrates lead to amido 2-sulfinyl butadiene derivatives in excellent yields, with total chemo- and diastereoselectivity. These amido dienyl sulfoxides undergo highly selective Diels-Alder cycloadditions with N-phenylmaleimide with remarkable stereocontrol by the sulfoxide moiety.

Synthesis of Enantiopure 3-Hydroxypiperidines from Sulfinyl Dienyl Amines by Diastereoselective Intramolecular Cyclization and [2,3]-Sigmatropic Rearrangement.

The highly diastereoselective base-promoted intramolecular cyclization of a variety of enantiopure sulfinyl dienyl amines provides novel sulfinyl tetrahydropyridines that are readily converted to 3-hydroxy tetrahydropyridines via sigmatropic rearrangement. The influence of N- and C- substituents on the process has been studied. Procedures to shorten the sequence such as the tandem cyclization followed by [2,3]-sigmatropic rearrangement, as well as cyclization of the free amine, under Boc- or ArSO- deprotection conditions have been examined.

Review cyclic peptides on a merry-go-round; towards drug design.

Peptides and proteins are attractive initial leads for the rational design of bioactive molecules. Several natural cyclic peptides have recently emerged as templates for drug design due to their resistance to chemical or enzymatic hydrolysis and high selectivity to receptors. The development of practical protocols that mimic the power of nature's strategies remains paramount for the advancement of novel peptide-based drugs.

Organocatalytic Michael addition-lactonisation of carboxylic acids using α,β-unsaturated trichloromethyl ketones as α,β-unsaturated ester equivalents.

Isothiourea HBTM-2.1 catalyses the Michael addition-lactonisation of 2-aryl and 2-alkenylacetic acids and α,β-unsaturated trichloromethyl ketones. Ring-opening of the resulting dihydropyranones and subsequent alcoholysis of the CCl3 ketone with an excess of methanol gives a range of diesters in high diastereo- and enantioselectivity (up to 95 : 5 dr and >99% ee).

Remote stereocontrol in the synthesis of acyclic 1,4-diols and 1,4-aminoalcohols from 2-sulfinyl dienes.

The highly diastereoselective conjugate addition of alcohols and amines (RXH) to enantiopure 2-sulfinyl dienes renders transient allylic sulfoxides which undergo sulfoxide-sulfenate rearrangement and sulfenate cleavage providing 2-ene-1,4-diols and 2-ene-1,4-aminoalcohols with up to 99:1 dr. The method allows for the generation of two stereocenters in a single synthetic operation with remote chirality transfer of one center into the other.

Sulfoxide-directed enantioselective synthesis of functionalized tetrahydropyridines.

The highly selective base-promoted cyclization of enantiopure sulfinyl dienamines provides stereodefined sulfinyl 1,2,3,6-tetrahydropyridines (dr up to 99:1). Subsequent sigmatropic rearrangement affords tetrahydropyridin-3-ols in good yields and selectivities.

Organocatalytic functionalization of carboxylic acids: isothiourea-catalyzed asymmetric intra- and intermolecular Michael addition--lactonizations.

Tetramisole promotes the catalytic asymmetric intramolecular Michael addition-lactonization of a variety of enone acids, giving carbo- and heterocyclic products with high diastereo- and enantiocontrol (up to 99:1 dr, up to 99% ee) that are readily derivatized to afford functionalized indene and dihydrobenzofuran carboxylates. Chiral isothioureas also promote the catalytic asymmetric intermolecular Michael addition-lactonization of arylacetic acids and α-keto-β,γ-unsaturated esters, giving anti-dihydropyranones with high diastereo- and enantiocontrol (up to 98:2 dr, up to 99% ee).

Leukocyte-technetium-99m uptake in Crohn's disease: does it show subclinical disease?

Aim: To evaluate inflammatory activity in patients with Crohn's disease (CD) using technetium-99m-hexamethylpropyleneamine oxime (99mTc-HMPAO) granulocyte scintigraphy.

Methods: Twenty patients (7 male and 13 female) with CD and five healthy volunteers were selected for 99mTc-HMPAO granulocyte scintigraphy. The Crohn's Disease Activity Index (CDAI), blood tests and C-reactive protein (CRP) of each patient were performed 7 d before the scintigraphic images.

General, stereoselective synthesis of (Z)-beta,gamma-unsaturated nitriles promoted by samarium diiodide.

A method to obtain (Z)-beta,gamma-unsaturated nitriles in high or good yields and with moderate or high stereoselectivity is described. The products were achieved through the photoinduced metalation of 3-acetoxy-4-chloronitriles with SmI2. The starting compounds were readily prepared, and a mechanism is proposed to explain this stereoselective beta-elimination reaction.

Addition reactions of iodomethyllithium to imines. A direct and efficient synthesis of aziridines and enantiopure amino aziridines.

An efficient and general synthesis of aziridines by the reaction of imines derived from p-toluenesulfonamides with in situ generated iodomethyllithium, with a simple and rapid experimental protocol, is reported for the first time. The reaction with the chiral aldimine derived from phenylalaninal allowed access to (2R,1'S)-2-(1'-aminoalkyl)aziridine with very high diastereoselectivity, in enantiopure form. A mechanism to explain this novel reaction is proposed.

Amidine catalysed O- to C-carboxyl transfer of heterocyclic carbonate derivatives.

The structural requirements of amidines necessary to act as efficient O- to C-carboxyl transfer agents are delineated and the scope of this process outlined through its application to a range of oxazolyl, benzofuranyl and indolyl carbonates.

The first cyclopropanation reaction of unmasked alpha,beta-unsaturated carboxylic acids: direct and complete stereospecific synthesis of cyclopropanecarboxylic acids promoted by Sm/CHI3.

A samarium-promoted cyclopropanation of unmasked alpha,beta-unsaturated acids is described. This reaction can be carried out on (E)- or (Z)-alpha,beta-unsaturated carboxylic acids. In all cases the process is completely stereospecific and stereoselective.