Search results for "Structure-Activity Relationship"
showing 10 items of 743 documents
Information Theoretic Entropy for Molecular Classification: Oxadiazolamines as Potential Therapeutic Agents
2013
In this review we present algorithms for classification and taxonomy based on information entropy, followed by structure-activity relationship (SAR) models for the inhibition of human prostate carcinoma cell line DU-145 by 26 derivatives of N-aryl-N-(3-aryl-1,2,4-oxadiazol-5-yl)amines (NNAs). The NNAs are classified using two characteristic chemical properties based on different regions of the molecules. A table of periodic properties of inhibitors of DU-145 human prostate carcinoma cell line is obtained based on structural features from the amine moiety and from the oxadiazole ring. Inhibitors in the same group and period of the periodic table are predicted to have highly similar propertie…
The inhibition by flavonoids of 2-amino-3-methylimidazo[4,5-f]quinoline metabolic activation to a mutagen: a structure-activity relationship study.
1997
The mutagenicity of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in Salmonella typhimurium TA98 is inhibited by flavonoids with distinct structure-antimutagenicity relationships (Edenharder, R., I. von Petersdorff I. and R. Rauscher (1993). Antimutagenic effects of flavonoids, chalcones and structurally related compounds on the activity of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and other heterocyclic amine mutagens from cooked food, Mutation Res., 287, 261-274). With respect to the mechanism(s) of antimutagenicity, the following results were obtained here. (1) 7-Methoxy- and 7-ethoxyresorufin-O-dealkylase activities in rat liver microsomes, linked to cytochrome P-450-dependent 1A1 and…
Clavines as antitumor agents. 3: Cytostatic activity and structure/activity relationships of 1-alkyl agroclavines and 6-alkyl 6-noragroclavines.
1986
The cytostatic potential of twenty antibiotic agroclavines has been examined in the L5178y mouse lymphoma cell system. Twelve of these compounds are described for the first time. It is shown that the substituent at N-1 of agroclavine is very important whereas the substituent at N-6 is of less influence if it is not hydrogen. Incorporation studies in the presence of 1-propylagroclavine suggest that DNA synthesis in the lymphoma cells is inhibited. The effect on the corresponding [3H]thymidine incorporation in murine spleen lymphocytes is comparably low. Neither a significant change of mRNA efflux nor of DNA polymerase alpha and beta activities was caused. The mechanism of action seems to be …
The Anti-amyloid Compound DO1 Decreases Plaque Pathology and Neuroinflammation-Related Expression Changes in 5xFAD Transgenic Mice
2018
Self-propagating amyloid-β (Aβ) aggregates or seeds possibly drive pathogenesis of Alzheimer's disease (AD). Small molecules targeting such structures might act therapeutically in vivo. Here, a fluorescence polarization assay was established that enables the detection of compound effects on both seeded and spontaneous Aβ42 aggregation. In a focused screen of anti-amyloid compounds, we identified Disperse Orange 1 (DO1) ([4-((4-nitrophenyl)diazenyl)-N-phenylaniline]), a small molecule that potently delays both seeded and non-seeded Aβ42 polymerization at substoichiometric concentrations. Mechanistic studies revealed that DO1 disrupts preformed fibrillar assemblies of synthetic Aβ42 peptides …
Inhibition of ethoxyresorufin deethylase activity by natural flavonoids in human and rat liver microsomes
1990
Several flavones and flavonols (chrysin, quercetin, luteolin, flavone and 7, 8-benzoflavone) were found to inhibit ethoxyresorufin deethylase (EROD) activity in human and rat liver microsomes. In man, molecules without hydroxyl groups are more powerful inhibitors than polyhydroxylated flavonoids (7, 8-benzoflavone greater than flavone greater than chrysin greater than luteolin greater than quercetin greater than morin). In rat, chrysin was the strongest inhibitor and the less effective were morin and 7,8-benzoflavone. For all molecules human microsomes were more sensitive than rat microsomes. The most important difference concerned 7,8-benzoflavone which was 10,000-fold more potent in man.
Regio- and stereo-selectivity in the induction of peroxisome proliferation by substituted hexanoic acids
1993
Summary Quantitative structure-activity relationship is an effective tool in order to predict drug potency. A similar approach is actually developed for peroxisome proliferation induced by substituted carboxylic acids issued from plasticizer metabolism in rats. The study is focused on acids found in rat urine after adipic diester dosings. Size, location of the substituted group and length of the chain have been studied. 3-D structure has also been taken in account for 2-ethyl hexanoic acids. The results obtained so far demonstrate that peroxisome proliferation potencies of the considered acids are modified according structure changes. At this time location of the group along the chain appea…
Organometallic complexes with biological molecules. XVII. Triorganotin(IV) complexes with amoxicillin and ampicillin.
2002
Novel triorganotin(IV) complexes of two β-lactamic antibiotics, 6-[D-(-)-β-amino-p-hydroxyphenyl-acetamido]penicillin (=amoxicillin) and 6-[D-(-)-α-aminobenzyl]penicillin (=ampicillin), have been synthesized and investigated both in solid and solution states. The complexes corresponded to the general formula R3Sn(IV)antib·H2O (R=Me, n-Bu, Ph; antib=amox=amoxicillinate or amp=ampicillinate). Structural investigations about configuration in the solid state have been carried out by interpreting experimental IR and 119Sn Mössbauer data. In particular, IR results suggested polymeric structures both for R3Sn(IV)amox·H2O and R3Sn(IV)amp·H2O. Moreover, both antibiotics appear to behave as monoanion…
2-sulfonyliminodihydropyrimidines: a novel class of analgesic compounds.
2008
A series of 2-sulfonyliminodihydropyrimidine derivatives have been synthesized and evaluated in vivo for their antinociceptive and anti-inflammatory activities. The results were compared with that of acetyl salicylic acid. Compounds 6Ab-d and 6Be displayed an interesting analgesic profile in the acetic acid-induced abdominal contractions test. Based on the results of the carrageenan-hind paw edema test, compound 6Af showed potential anti-inflammatory activity.
Phenotypic and biochemical analysis of an international cohort of individuals with variants in NAA10 and NAA15.
2019
Abstract N-alpha-acetylation is one of the most common co-translational protein modifications in humans and is essential for normal cell function. NAA10 encodes for the enzyme NAA10, which is the catalytic subunit in the N-terminal acetyltransferase A (NatA) complex. The auxiliary and regulatory subunits of the NatA complex are NAA15 and Huntington-interacting protein (HYPK), respectively. Through a genotype-first approach with exome sequencing, we identified and phenotypically characterized 30 individuals from 30 unrelated families with 17 different de novo or inherited, dominantly acting missense variants in NAA10 or NAA15. Clinical features of affected individuals include variable levels…
Δ5-Cholenoyl-amino acids as selective and orally available antagonists of the Epheephrin system
2015
The Eph receptor-ephrin system is an emerging target for the development of novel anti-angiogenic therapies. Research programs aimed at developing small-molecule antagonists of the Eph receptors are still in their initial stage as available compounds suffer from pharmacological drawbacks, limiting their application in vitro and in vivo. In the present work, we report the design, synthesis and evaluation of structure-activity relationships of a class of Δ(5)-cholenoyl-amino acid conjugates as Eph-ephrin antagonists. As a major achievement of our exploration, we identified N-(3β-hydroxy-Δ(5)-cholen-24-oyl)-L-tryptophan (UniPR1331) as the first small molecule antagonist of the Eph-ephrin syste…