Active Amino Acid Derivatives Research Articles

Synthesis, fungicidal activity and SAR of new amino acid derivatives containing substituted 1-(phenylthio)propan-2-amine moiety

Fifteen novel amino acid derivatives were designed and synthesized using natural amino acid L-valine and two non-natural amino acids as raw materials. Fungicidal activities of these amino acid derivatives were tested against Phytophthora capsici. Most of these compounds possessed excellent activity against Phytophthora capsici at 50 μg/mL. Interestingly, compound isopropyl ((2S)-1-((1-((4-fluorophenyl)thio)propan-2-yl)amino)-3-methyl-1-oxobutan-2-yl)carbamate 5c (EC50=0.43 μg/mL), isopropyl ((2S)-1-((1-((3,4-dimethoxyphenyl)thio)propan-2-yl)amino)-3-methyl-1-oxobutan-2-yl)carbamate 5g (EC50=0.49 μg/mL), isopropyl ((2S)-1-((1-((4-(ethynyloxy)phenyl)thio)propan-2-yl)amino)-3-methyl-1-oxobutan-2-yl)carbamate 5h (EC50=0.15 μg/mL) and isopropyl ((2S,3S)-1-((1-((4-(ethynyloxy)phenyl)thio)propan-2-yl)amino)-3-methyl-1-oxopentan-2-yl)carbamate 5o (EC50=0.31 μg/mL) exhibited remarkably high activities against Phytophthora capsici, which is better than that of positive control. It is possible that these amino acid derivatives, which possess excellent activity against Phytophthora capsici, may become novel lead compounds for the development of fungicides with further structure modification.

Mechanism of the Antioxidant Activity and Structure\u2013Activity Relationship of N-Monosubstituted Amino Acid Derivatives of Fullerene \u042160

The kinetic characteristics, mechanisms of activity, and relationship between the antioxidant activity and the molecular and supramolecular structure of fullerene C60 and some of its N-monosubstituted amino acid derivatives have been studied. The introduction of an amino acid substituent in the C60 fullerene molecule led to an increase in its antiradical activity in the free radical oxidation of a water-soluble target (fluorescein). The mechanism of the antioxidant activity of amino acid derivatives of fullerene is not associated with the hydrogen atom transfer, electron donation, or catalysis of peroxide decomposition. It was demonstrated that the structure of the amino acid substituent does not affect the antiradical properties, which are thus determined only by the effective total surface area of ​​the nanoparticles of the fullerene C60 derivatives and increase when their size decreases. This surface can be characterized as nanowalls on which the radical death occurs. A change in the concentration of the compounds in solution does not lead to a change in the relative antiradical activity and hence in the nanoparticle size. The results of this study are important for understanding the biological activity of this group of compounds.

Research in vivo the qualities of potential antitumor amino-acid derivatives of glycosides of indolocarbazol

Background. The addition of active metabolites (in particular, amino acids) to the molecule affects the physicochemical and prodrug properties of derivatives of indolocarbazoles. Using computed chemoinformatics, probability antitumor activity of amino-acid derivatives of glycosides of indolocarbazol (AADGI) is predicted with low probability of their cytotoxic activity in vitro. Based on these data, a study of these compounds in vivo is conducted. Objective: the assessment of AADGI as potential antitumor medications. Materials and methods. Research antitumor activity of AADGI was done using murine tumor models - cervical cancer CC-5. Investigated compounds were injected to mice СВА abdominally 5-times daily with interval of 24 h. Observation of animals were continued till their death. Antitumor effect of compounds was assessed by criteria of tumor growth inhibition and increase in life expectancy of mice comparing to control animals. Results. The optimal dose for these series of compounds was titrated and this dose is 100 mg/kg. Antitumor activity of AADGI was assessed on CC-5. Conclusions. Based on data received we suggest an extended study in vivo of antitumor qualities of selected 5 leader AADGI.

Synthesis and antimicrobial activity of amino acid and peptide derivatives of mycophenolic acid

The series of 16 novel amino acid and peptide mycophenolic acid (MPA) derivatives was obtained as potential antibacterial agents. Coupling of MPA with respective amines was optimized with condensing reagents such as EDCI/DMAP and T3P/TEA. Amino acid analogs were received both as methyl esters and also with the free carboxylic group. The biological activity of the products was tested on five references bacterial strains: Klebsiella pneumoniae ATCC 700603 (ESBL), Escherichia coli ATCC 8739, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus MRSA ATCC 43300, Staphylococcus aureus MSSA ATCC 25923. Peptide derivatives proved to be the most versatile ones, their MIC values relative to most strains was lower than MPA alone. It has been noted that the activity of amino acid derivatives depends on the configuration at the chiral center in the amino acid unit and methyl esters indicated better antimicrobial activity than analogs with free carboxylic group.

Isolation and antioxidative activity of amino acid derivatives produced by Leuconostoc mesenteroides.

One new phenyl lactic acid derivative, N-(5-amino-2-hydroxy-1-oxopentyl)-tyrosine (2), and three known metabolites [(S)-8-hydroxy-4-hydroxy-phenylpropanoic acid (1), (S)-8-hydroxy-phenylpropanoic acid (3), and indole-(S)-3-lactic acid (4)] were isolated from the culture medium of Leuconostoc mesenteroides guided with DPPH radical-scavenging assay. The chemical structures of the isolated compounds were determined by NMR and electrospray ionization mass spectroscopy. The isolated four compounds were assumed to be metabolites formed by the transformation of amino acids. The DPPH radical-scavenging activities of 1 and 2 were significantly higher than those of 3 and 4. This result may provide meaningful information of antioxidative metabolites from lactic acid bacteria.

Synthesis and biological activity of amino acid derivatives of avarone and its model compound

A series of eighteen derivatives of marine sesquiterpene quinone avarone and its model system tert-butylquinone with amino acids has been synthesized by nucleophilic addition of amino acids to the quinones. In vitro cytotoxic activity toward human cancer cell lines (HeLa, A549, Fem-X, K562, MDA-MB-453) and normal MRC-5 cell line was determined. Several compounds showed very strong inhibitory activity with IC50 values less than 10μM. Avarone derivatives were more active than the corresponding tert-butylquinone derivatives. The results of the cytofluorimetric analysis of cell cycle of HeLa cells showed that apoptosis might be one of possible mechanism of action of these compounds in cancer cells. In order to examine the influence of caspases on cell death, the apoptotic mechanisms induced by the tested compounds were determined using specific caspases 3, 8 and 9 inhibitors. For all compounds antibacterial activities against six strains of Gram-positive and four strains of Gram-negative bacteria were determined, as well as antifungal activity against three fungal species.

SLC36A4 (hPAT4) Is a High Affinity Amino Acid Transporter When Expressed in Xenopus laevis Oocytes

The SLC36 family of transporters consists of four genes, two of which, SLC36A1 and SLC36A2, have been demonstrated to code for human proton-coupled amino acid transporters or hPATs. Here we report the characterization of the fourth member of the family, SLC36A4 or hPAT4, which when expressed in Xenopus laevis oocytes also encodes a plasma membrane amino acid transporter, but one that is not proton-coupled and has a very high substrate affinity for the amino acids proline and tryptophan. hPAT4 in Xenopus oocytes mediated sodium-independent, electroneutral uptake of [(3)H]proline, with the highest rate of uptake when the uptake medium pH was 7.4 and an affinity of 3.13 μM. Tryptophan was also an excellently transported substrate with a similarly high affinity (1.72 μM). Other amino acids that inhibited [(3)H]proline were isoleucine (K(i) 0.23 mM), glutamine (0.43 mM), methionine (0.44 mM), and alanine (1.48 mM), and with lower affinity, glycine, threonine, and cysteine (K(i) >5 mM for all). Of the amino acids directly tested for transport, only proline, tryptophan, and alanine showed significant uptake, whereas glycine and cysteine did not. Of the non-proteogenic amino acids and drugs tested, only sarcosine produced inhibition (K(i) 1.09 mM), whereas γ-aminobutyric acid (GABA), β-alanine, L-Dopa, D-serine, and δ-aminolevulinic acid were without effect on [(3)H]proline uptake. This characterization of hPAT4 as a very high affinity/low capacity non-proton-coupled amino acid transporter raises questions about its physiological role, especially as the transport characteristics of hPAT4 are very similar to the Drosophila orthologue PATH, an amino acid "transceptor" that plays a role in nutrient sensing.

Synthesis of Optically Active Amino Acid Derivatives via Dynamic Kinetic Resolution

The complete conversion of racemic amino acid amides to optically active amino acid derivatives was accomplished via lipase/palladium-catalyzed dynamic kinetic resolution (DKR). In the DKR, a lipase catalyzes the selective acylation of L-substrate in the presence of acyl donor while unreacted D-substrate is isomerized by a Pd nanocatalyst to L-substrate. The DKR reactions provided good yields (80-98%) and high enantiomeric excess (95-98% ee). Interestingly, the DKR reactions of phenylglycine amide in the presence of Z-Gly-OMe or Z-Gly-Gly-OMe yielded optically active di- and tripeptide .

Substrate specificity of the amino acid transporter PAT1

The proton coupled amino acid transporter PAT1 expressed in intestine, brain, and other organs accepts L- and D-proline, glycine, and L-alanine but also pharmaceutically active amino acid derivatives such as 3-amino-1-propanesulfonic acid, L-azetidine-2-carboxylic acid, and cis-4-hydroxy-D-proline as substrates. We systematically analyzed the structural requirements for PAT1 substrates by testing 87 amino acids, proline homologs, indoles, and derivatives. Affinity data and effects on membrane potential were determined using Caco-2 cells. For aliphatic amino acids, a blocked carboxyl group, the distance between amino and carboxyl group, and the position of the hydroxyl group are affinity limiting factors. Methylation of the amino group enhances substrate affinity. Hetero atoms in the proline template are well tolerated. Aromatic alpha-amino acids display low affinity. PAT1 interacts strongly with heterocyclic aromatic acids containing an indole scaffold. The structural requirements of PAT1 substrates elucidated in this study will be useful for the development of prodrugs.

Synthesis, Characterization, and Biological Activity of Amino Acid Derivatives of the Heteropolytungstophosphoric Acid

Compounds of phosphotungstic acid (WPA) containing the amino acids alanine (WPA–Ala) or glycine (WPA–Gly) as counter cations were synthesized and characterized by elemental analysis, thermal analysis, and IR spectroscopy. Cellular toxicity was assessed by the trypan blue exclusion method, and the antiviral activity of WPA and the modified WPA compounds was tested against herpes simplex viruses (HSV) type 1 and type 2. Biological assays indicate that the newly synthesized compounds exhibit no evident cytotoxic effects on Vero cells and negligible antiviral activity against HSV-1 and HSV-2.

Antibody-Mimicking Polymers as Chiral Stationary Phases in HPLC

Antibody-mimicking synthetic polymers, selective for various optically active amino acid derivatives and peptides, were prepared by noncovalent molecular imprinting. A novel approach, in which the branched, trifunctional cross-linkers pentaerythritol triacrylate and 2,2-bis(hydroxymethyl)butanol trimethacrylate were copolymerized with methacrylic acid, is described. The polymers were subsequently applied as chiral stationary phases in high-performance liquid chromatography. They were superior to previously reported noncovalent molecularly imprinted polymers used for chiral separations in that they showed considerably higher load capacity, increased selectivity, and better resolving capability.

Synthese und Eigenschaften von Makrocyclen aus Resorcinen sowie von entsprechenden Derivaten und Wirt‐Gast‐Komplexen

Synthesis and Properties of Macrocycles from Resorcinol, Corresponding Derivatives and Host‐Guest ComplexesStructural variations of the metacyclophanes obtained from the condensation of resorcinol with aldehydes RCHO are described, mostly based on the stereoisomer with all R in cis configuration. The basic tetraphenolate (with R = CH3, 1a) shows a cone‐conformation as evident e.g. from vicinal 13C–C–C–1H coupling constants. Substituents R′ in the 2‐position of the phenyl rings at the upper rim of the macro‐cycle are either introduced with the resorcinol derivative used (R′ = CH3, COOH), or by Mannich reactions after cyclization (R′ = CH2NR″2), which partially lead to intermediate oxacine formation. Acid‐base properties are evaluated with potentiometric and NMR‐shift titrations. Mannich products from amino acids such as proline, which are formed without racemization, show no pK differences for the groups at the four equivalent phenyl rings, but three distinct pK values for the deprotonation of OH, COOH, and +NH3 substituents; the pK of the latter is two units lower than in proline itself as it is involved in hydrogen bridging. Complexation constants K of such derivatives with Fe3+, Cu2+, and Zn2+ show the expected increase with metal ion acidity; they are increased by a power of 5 in comparison to proline. Complexation constants and complexation‐induced NMR shifts (CIS values) are determined for 51 complexes, with positively charged organic guest molecules for the basic tetraphenolate skeleton as well as for the aminomethylation derivatives. A temperature dependence study shows that the corresponding equilibrium is driven by ΔH with negligible ΔS contributions. No chiral discrimation is observed upon complexation of e.g. carnitine with the optically active amino acid derivatives. This is in line with CIS and K values obtained with several complexes showing an orientation of the NR″2 groups away from the cavity. The COOH substituents R′ form strong hydrogen bonds with the adjacent phenolic groups, leading to alternating pseudo‐eq and ‐ax positions of the phenyl rings. Their interconversion barrier, determined by NMR spectroscopy, is 72 kJ mol‐1; they bind mono‐ and bis‐ammonium ions as function of distance matching. The presence of lipophilic substituents (R = phenyl, benzyl, biphenyl, n‐hexyl, n‐undecyl) at the bottom of the macrocycle furnishes a second binding center which allows to complex e.g. diethyl ether in water. Coordination of zinc to the proline derivative still allows co‐complexation of choline acetate, the hydrolysis of which is not inhibited anymore as it is by the zinc‐free macrocycle.

Synthesis and pharmacological activity of amino acid derivatives of nicotinic acid

Synthesis and pharmacological activity of amino acid derivatives of nicotinic acid

ChemInform Abstract: Synthesis and Antitumor Activity of Amino Acid Derivatives of the Antimetastatic Agent DM‐COOK.

ChemInformVolume 19, Issue 50 Isocyclic Compounds ChemInform Abstract: Synthesis and Antitumor Activity of Amino Acid Derivatives of the Antimetastatic Agent DM-COOK. L. LASSIANI, L. LASSIANI Ist. Chim. Farm., Univ., Trieste, ItalySearch for more papers by this authorM. M. DE NARDO, M. M. DE NARDO Ist. Chim. Farm., Univ., Trieste, ItalySearch for more papers by this authorC. NISI, C. NISI Ist. Chim. Farm., Univ., Trieste, ItalySearch for more papers by this authorA. VARNAVAS, A. VARNAVAS Ist. Chim. Farm., Univ., Trieste, ItalySearch for more papers by this author L. LASSIANI, L. LASSIANI Ist. Chim. Farm., Univ., Trieste, ItalySearch for more papers by this authorM. M. DE NARDO, M. M. DE NARDO Ist. Chim. Farm., Univ., Trieste, ItalySearch for more papers by this authorC. NISI, C. NISI Ist. Chim. Farm., Univ., Trieste, ItalySearch for more papers by this authorA. VARNAVAS, A. VARNAVAS Ist. Chim. Farm., Univ., Trieste, ItalySearch for more papers by this author First published: December 13, 1988 https://doi.org/10.1002/chin.198850125Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume19, Issue50December 13, 1988 RelatedInformation

Separation of enantiomers in thin-layer chromatography

Up to now in thin-layer chromatography a series of retention mechanisms for the determination of enantiomeric compositions have been applied. Subject of this paper is a corresponding survey with a focal point on ligand exchange chromatography. In connection with this retention mechanism most successfully used in TLC for the separation of optical antipodes, some additional findings of the authors are included. Retention mechanisms in question are: - Formation of inclusion complexes within the cavities of cyclodextrins. Substance classes separated by this system are e.g. dansyl amino acids or metallocenes. - Interaction with so-called “brush type” phases. In this case, chiral groups with π-acceptor of π-donor properties are chemically or physically bonded to an aminomodified silica gel matrix. Chiral compounds, like aromatic alcohols, were separated on these stationary phases. - Differences in retention of diastereomers formed previously or during the chromatographic process on an achiral stationary phase. Some examples for the manifold applicability of this principle are the separation of chiral amines from biological matrices, hydroxy-fatty acids, and amino acids. - Selective interactions with the helical structures of cellulose or cellulose triacetate. Referring to this technique, separations of several amino acids and of the analgesic agent Oxidanac in the R-and S-species are described. - Enantioselective ligand exchange, based on reversed phase silica gels impregnated with copper salts and optically active amino acid derivatives. In thin-layer chromatography this is the most important principle used mainly for the separation of racemic mixtures of free amino acids and amino acid derivatives. The recently developed HPTLC pre-coated plate CHIR with concentrating zone is also based on this retention mechanism. Aside from the applications mentioned above, dipeptides, hydroxy-carboxylic acids, α-halogenated carboxylic acids, amino lactones, and thiazolidine derivatives have been separated on this plate up to now. Furthermore, this new pre-coated layer is particularly suitable for an optical in situ evaluation and quantitative determinations of optical antipodes.

P-385 - Studies on anti-diabetic activity of amino acid derivatives (III) Hypoglycemic effect of N-(trans-4-alkylcyclohexylcarbonyl)-D-phenylalanines

P-385 - Studies on anti-diabetic activity of amino acid derivatives (III) Hypoglycemic effect of N-(trans-4-alkylcyclohexylcarbonyl)-D-phenylalanines

O-299 - Studies on anti-diabetic activity of amino acid derivatives (II) Hypoglycemic effect of phenylalanine derivatives and N-Benzoyl-D-phenylalanine

O-299 - Studies on anti-diabetic activity of amino acid derivatives (II) Hypoglycemic effect of phenylalanine derivatives and N-Benzoyl-D-phenylalanine

Synthesis and biological activity of amino acid derivatives of sulfanilic acid

Synthesis and biological activity of amino acid derivatives of sulfanilic acid

P-222 - Studies on anti-diabetic activity of amino acid derivatives (I) Relation between chemical structures and pharmacological effects

P-222 - Studies on anti-diabetic activity of amino acid derivatives (I) Relation between chemical structures and pharmacological effects

Studies on the anti-diabetic activity of amino acid derivatives.(1)

Studies on the anti-diabetic activity of amino acid derivatives.(1)