Search results for "Structure-Activity Relationship"

Bond-based 3D-chiral linear indices: Theory and QSAR applications to central chirality codification

2008

The recently introduced non-stochastic and stochastic bond-based linear indices are been generalized to codify chemical structure information for chiral drugs, making use of a trigonometric 3D-chirality correction factor. These improved modified descriptors are applied to several well-known data sets to validate each one of them. Particularly, Cramer's steroid data set has become a benchmark for the assessment of novel quantitative structure activity relationship methods. This data set has been used by several researchers using 3D-QSAR approaches such as Comparative Molecular Field Analysis, Molecular Quantum Similarity Measures, Comparative Molecular Moment Analysis, E-state, Mapping Prope…

(Strept)avidin as host for biotinylated coordination complexes: stability, chiral discrimination, and cooperativity

2005

Incorporation of a biotinylated ruthenium tris(bipyridine) [Ru(bpy)₂(Biot-bpy)]²⁺ (1) in either avidin or streptavidin-(strept)avidin-can be conveniently followed by circular dichroism spectroscopy. To determine the stepwise association constants, cooperativity, and chiral discrimination properties, diastereopure (Λ and δ)-1 species were synthesized and incorporated in tetrameric (strept)avidin to afford (δ-[Ru(bpy)₂(Biot-bpy)]²⁺)x⊂avidin, (Λ- [Ru(bpy)₂(Biot-bpy)]²⁺)x⊂avidin, (δ-[Ru(bpy)₂(Biot- bpy)]²⁺)x⊂streptavidin, and (Λ-[Ru(bpy)₂(Biot-bpy)]²⁺) x⊂streptavidin (x = 1-4) For these four systems, the overall stability constants are log β₄ = 28.6, 30.3, 36.2, and 36.4, respectively. Critical…

Mutations affecting MHC class II binding of the superantigen streptococcal erythrogenic toxin A.

1993

Streptococcal pyrogenic exotoxin A (SPEA) is an important pathogenicity factor of group A streptococci. It is a member of the family of 'superantigens' produced by Staphylococcus aureus and Streptococcus pyogenes, and its T lymphocyte stimulating activity is involved in the pathogenesis of certain diseases caused by pyogenic streptococci. In this study we have generated nine mutant SPEA molecules by substituting amino acids in the regions of homology between different streptococcal and staphylococcal superantigens. An additional mutant was created by deletion of the 10 N-terminal amino acids. The mutants were expressed as fusion proteins. Several mutations led to a loss of function due to a…

To Hit or Not to Hit, That Is the Question - Genome-wide Structure-Based Druggability Predictions for Pseudomonas aeruginosa Proteins.

2015

Pseudomonas aeruginosa is a Gram-negative bacterium known to cause opportunistic infections in immune-compromised or immunosuppressed individuals that often prove fatal. New drugs to combat this organism are therefore sought after. To this end, we subjected the gene products of predicted perturbative genes to structure-based druggability predictions using DrugPred. Making this approach suitable for large-scale predictions required the introduction of new methods for calculation of descriptors, development of a workflow to identify suitable pockets in homologous proteins and establishment of criteria to obtain valid druggability predictions based on homologs. We were able to identify 29 pert…

Acid- and Base-Catalysis in the Mononuclear Rearrangement of Some (Z)-arylhydrazones of 5-Amino-3-benzoyl-1,2,4-oxadiazole in Toluene: Effect of Subs…

2011

The reaction rates for the rearrangement of eleven (Z)-arylhydrazones of 5-amino-3-benzoyl-1,2,4-oxadiazole 3a-k into the relevant (2-aryl-5-phenyl-2H-1, 2,3-triazol-4-yl)ureas 4a-k in the presence of trichloroacetic acid or of piperidine have been determined in toluene at 313.1 K. The results have been related to the effect of the aryl substituent by using Hammett and/or Ingold-Yukawa-Tsuno correlations and have been compared with those previously collected in a protic polar solvent (dioxane/water) as well as with those on the analogous rearrangement of the corresponding (Z)-arylhydrazones of 3-benzoyl-5-phenyl-1,2,4-oxadiazole 1a-k in benzene. Some light can thus be shed on the general di…

Synthesis and Spectral and Structural Characterization of a New Series of Bis-Strapped Chiral Porphyrins Derived from L-Proline

2001

International audience; New chiral porphyrins were obtained in reasonable yields in three steps, starting from the áâáâ atropisomer of mesotetrakis(o-aminophenyl)porphyrin (TAPP). These potential catalysts for the enantioselective epoxidation of alkenes were obtained by the reaction of different linkers on the same Lprolinoyl-picket porphyrin. Their 1H NMR spectral characteristics, as well as the crystal structure of one of them, clearly indicate that the orientation of the proline cycle depends on the linker used to tether the two pickets on each side of the porphyrin. The same linker is employed for both sides of the porphyrin; hence the resulting D2-symmetric superstructure.

Cytotoxic geranylflavonoids from Bonannia graeca

2011

The analysis of the aerial parts of Bonannia graeca led to the isolation and characterization of two new polar geranylated flavonoids (6 and 7). The structure elucidation was performed by extensive spectroscopic methods (1D and 2D NMR) and comparison with literature data. All natural flavonoids isolated from B. graeca (1–7) and some synthetic derivatives (8–11) were tested for cytotoxic activity against four human tumor cell lines. Preliminary structure-activity relationship correlations are discussed.

Design, synthesis, and biological evaluation of novel aminobisphosphonates possessing an in vivo antitumor activity through a gammadelta-T lymphocyte…

2008

A small series of aminobisphosphonates (N-BPs) structurally related to zoledronic acid was synthesized with the aim of improving activity toward activation of human gammadelta T cells and in turn their in vivo antitumor activity. The absence of the 1-OH moiety, together with the position and the different basicity of the nitrogen, appears crucial for antitumor activity. In comparison to zoledronic acid, compound 6a shows a greater ability to activate gammadelta T cells expression (100 times more) and a proapoptotic effect that is better than zoledronic acid. The potent activation of gammadelta T cells, in addition to evidence of the in vivo antitumor activity of 6a, suggests it may be a new…

Differential mode of inhibition of terminal deoxynucleotidyl transferase by 3′-dATP, ATP, βaraATP and αaraATP

1978

Multidrug resistance reverting activity and antitumor profile of new phenothiazine derivatives

2008

Abstract A series of easily affordable phenothiazine derivatives bearing a rigid but-2-ynyl amino side chain were synthesized and tested to evaluate the MDR reverting activity and full antitumor profile. Some compounds endowed with remarkable MDR reverting effect were identified, and the most active one ( 6c ) was shown to increase doxorubicin retention in multidrug resistant cells, suggesting a direct interaction with P-glycoprotein. Furthermore, a broad range of cellular activities were observed for different compounds. In particular, the ability of some derivatives to induce antiproliferative effects on resistant cell lines and to interfere with the G 1 phase of the cell cycle, a phase u…