Organic and Medicinal Chemistry Letters最新文献

Background: Several species of the genus Launaea are used in folk medicine such as in bitter stomachic, skin diseases, and reported to have antitumor, insecticide, and cytotoxic activities. The antimicrobial activities of coumarin constituents and the neuropharmacological properties have been investigated as well. In this study, the chemical composition of essential oils from Launaea resedifolia L. has been identified using the ordinary GC-MS technique to reveal the presence of 19 compounds dominated by dioctyl phthalate. Moreover, the antibacterial activity of the crude oil has been carried out using disk diffusion method against seven bacteria strains.

Results: Nineteen compounds of essential oil of L. resedifolia L. were identified, representing 86.68% of the total oil. The compounds were identified by spectral comparison to be mainly esters, alcohols, ketones, and terpenes. The principal constituents are dioctyl phthalate (39.84%), Decanoic acid, decyl ester (12.09%), 11-Octadecenal (11.24%), and Eucalyptol (07.31%), while others were present in relatively small amounts. As far as antibacterial essays are concerned, it was found that the oils are active against most of the tested bacterial strains.

Conclusion: A major constituent in visible parts was Dioctyl phthalate (39.84%) and the yield of essential oils was 0.9%. These extracts reveal in vitro antibacterial activity on the studied bacterial, confirmed by the inhibition zone diameter ranging from 11 to 37 mm and a MIC value between 0.09 and 0.69 depending on the microorganism being tested.

Investigation of the aerial parts of the Egyptian medicinal plant Ammi majus L. led to isolation of new coumarin, 6-hydroxy-7-methoxy-4 methyl coumarin (2) and 6-hydroxy-7-methoxy coumarin (3); this is the first time they have been isolated from this plant. The structures of the compounds (2 &3) were elucidated by spectroscopic data interpretation and showed anti-inflammatory and anti-viral activity. GRAPHICAL An efficient, one-new coumarin (2) was isolated from the aerial parts of the A. Majus L. was evaluated for their anti-viral and anti-inflammatory activities.

Background: Thiazolidine-2, 4-diones (TZDs) have become a pharmacologically important class of heterocyclic compounds since their introduction in the form of glitazones into the clinical use for the treatment of type 2 diabetes. TZDs lower the plasma glucose levels by acting as ligands for gamma peroxisome proliferators-activated receptors. In addition, this class of heterocyclic compounds possesses various other biological activities such as antihyperglycemic, antimicrobial, anti-inflammatory, anticonvulsant, insecticidal, etc. TZDs are also known for lowering the blood pressure thereby reducing the chances of heart failure and micro-albuminuria in the patients with type 2 diabetes.

Results: We have described herein the synthesis of three series of compounds, namely, ethyl 2-((Z)-5-((3-aryl-1-phenyl-1H-pyrazol-4-yl)methylene)-2, 4-dioxothiazolidin-3-yl)acetates (4), methyl 2-((Z)-5-((3-aryl-1-phenyl-1H-pyrazol-4-yl)methylene)-2, 4-dioxothiazolidin-3-yl)acetates (5), and 2-((Z)-5-((3-aryl-1-phenyl-1H-pyrazol-4-yl)methylene)-2, 4-dioxothiazolidin-3-yl)acetic acids (6). The compounds 4 and 5 were synthesized by Knoevenagel condensation between 3-aryl-1-phenyl-1H-pyrazole-4-carbaldehydes (1) and ethyl/methyl 2-(2, 4-dioxothiazolidin-3-yl)acetates (3, 2) in alcohol using piperidine as a catalyst. The resultant compounds 4 and 5 having ester functionality were subjected to acidic hydrolysis to obtain 6. All the new compounds were tested for their in vitro antibacterial and antifungal activity.

Conclusions: Knoevenagel condensation approach has offered an easy access to new compounds 4-6. Antimicrobial evaluation of the compounds has shown that some of the compounds are associated with remarkable antifungal activity. In case of antibacterial activity, these were found to be effective against Gram-positive bacteria. However, none of the compounds were found to be effective against Gram-negative bacteria.

The protein kinase A (PKA)-catalyzed phosphorylation of peptide substrate RRASVA analogs, containing Nβ-Me-aza-β3-amino acid residues in all subsequent positions, was studied. This work follows along the lines of our previous research of the phosphorylation of aza-β3-analogs of RRASVA (the shortest active substrate of PKA) and allows characterizing the influence of Nβ-methylation of aza-β3-amino acid residues on substrate recognition by PKA on substrate binding and phosphorylation steps. It was found that the effect of Nβ-methylation was dependent upon the position of the structure alteration. Moreover, the presence of a single Nβ-methylation site in the substrate changed the recognition pattern of this series of peptidomimetics, strongly affecting the phosphorylation step. Structure modeling of aza-β3- and Nβ-Me-aza-β3-containing substrates revealed that Nβ-methylation of aza-β3-moieties changed the peptide bond geometry from trans- to cis-configuration in -CO-NMe- fragments, with an exception for the N-terminally methylated Nβ-Me-aza-β3-RRRASVA (with the N-terminal amino group not participating in the peptide bond) and RRAS-Nβ-Me-aza-β3-VA. As has been shown in literature, this conformational preference of the backbone has a significant influence on the flexibility of the peptide substrate chain. Following our results, this property seems to have significant influence on the recognition of the amino acid side groups by the enzyme binding site, and in the case of PKA this structural modification was decisive for the phosphate transfer step of the catalytic process.

Background: In our continued search for bioactive compounds from plants, conscious effort is being made to rapidly analyze ethnobotanical plants used for treating various ailments by traditional healers before this information is irrevocably lost as societies advance and rural communities become urbanized.

Results: A compound isolated from the aqueous extract of Pavetta crassipes leaves showed activity against some pathogenic microorganisms which included Streptococcus pyogenes, Corynebacterium ulcerans, Klebsiella pneumoniae, Neisseria gonorrhoeae, Pseudomonas aeruginosa, and Escherichia coli at a concentration < 50 mg/mL. The compound had minimum inhibitory concentration ranging from 6.25 to 12.5 mg/mL and minimum bactericidal concentration ranging from 12.5 to 25 mg/mL. The compound was identified using 1D and 2D NMR experiments and comparison with literature data as quercetin-3-O-rutinoside.

Conclusions: This has supported the ethnomedicinal use of the plant, confirmed its activity, and has also provided an easy and simple method for isolating this compound which has a lot of pharmaceutical and cosmetic applications from a new source.

Background: Apoptosis is known as programmed cell death that plays an important role in tumor biology.

Methods: In this study, apoptosis-inducing activity is predicted by using a QSAR modeling approach for a series of 4-anilinoquinozaline derivatives. 2D-QSAR model for the prediction of apoptosis-inducing activity was obtained by applying multiple linear regression giving r2 = 0.8225 and q2 = 0.7626, principal component regression giving r2 = 0.7539 and q2 = 0.6669 and partial least squares giving r2 = 0.8237 and q2 = 0.6224.

Results: QSAR study revealed that alignment-independent descriptors and distance-based topology index are the most important descriptors in predicting apoptosis-inducing activity. 3D-QSAR study was performed using k-nearest neighbor molecular field analysis (kNN-MFA) approach for both electrostatic and steric fields. Three different kNN-MFA 3D-QSAR methods (SW-FB, SA, and GA) were used for the development of models and tested successfully for internal (q2 > 0.62) and external (predictive r2 > 0.52) validation criteria. Thus, 3D-QSAR models showed that electrostatic effects dominantly determine the binding affinities.

Conclusions: The QSAR models developed in this study would be useful for the development of new apoptosis inducer as anticancer agents.

Background: Synthesis of oximes is an important reaction in organic chemistry, because these versatile oximes are used for protection, purification, and characterization of carbonyl compounds. Nitriles, amides via Beckmann rearrangement, nitro compounds, nitrones, amines, and azaheterocycles can be synthesised from oximes. They also find applications for selective α-activation. In inorganic chemistry, oximes act as a versatile ligand.Several procedures for the preparation of oximes exist, but, most of them have not addressed the green chemistry issue. They are associated with generation of pollutants, requirement of high reaction temperature, low yields, lack of a generalized procedure, etc. Hence, there is a demand for developing an efficient, convenient, and non-polluting or less polluting alternative method for the preparation of oximes. In this context, bismuth compounds are very useful as they are cheap in general, commercially available, air stable crystalline solids, safe, and non-toxic, hence easy to handle.

Results: Carbonyl compounds (aliphatic, heterocyclic, and aromatic) were converted into the corresponding oximes in excellent yields by simply grinding the reactants at room temperature without using any solvent in the presence of Bi2O3. Most importantly, this method minimizes waste disposal problems, provides a simple yet efficient example of unconventional methodology and requires short time.

Conclusions: We have developed a novel, quick, environmentally safe, and clean synthesis of aldoximes and ketoximes under solvent-free grinding condition.

Background: The classical Strecker reaction is one of the simplest and most economical methods for the synthesis of racemic α-aminonitriles (precursor of α-amino acids) and pharmacologically useful compounds.

Results: Indium powder in water is shown to act as a very efficient catalyst for one-pot, three-component synthesis of α-aminonitriles from diverse amines, aldehydes and TMSCN. This general rapid method is applicable to a wide range of amines and aldehydes and produces products in excellent yield.

Conclusions: The present one-pot, three-component environmentally benign procedure for the synthesis of α-aminonitriles will find application in the synthesis of complex biologically active molecules.

An efficient, one-pot synthesis was developed for 3-aminoalkylated indoles by three-component coupling reaction of aldehydes, N-methylanilines, and indoles using AgOTf as a catalyst. A series of twenty 3-aminoalkylated indoles was evaluated for their antibacterial activities against both Gram negative and Gram positive bacteria. Compounds 4b and 4r showed good antibacterial activity against both Gram positive and Gram negative strains. However, inversing the property of substituent (from 4r to 4q) resulted in the significant fall in the magnitude of antibacterial activity against Escherichia coli.

Novel 1,1'-(5,5'-(1,4-phenylene)bis(3-aryl-1H-pyrazole-5,1-(4H,5H)-diyl))diethanones 7-12 were tested for their antimicrobial activity by disc diffusion and twofold serial dilution method against the tested bacterial and fungal strains. Compounds 7 against Micrococcus luteus, 8 against β-Heamolytic streptococcus, M. luteus, Klebsiella pneumonia, Microsporum gypseum, 9 against Staphylococcus aureus, Shigella flexneri, Vibreo cholerae, Pseudomonas aeruginosa, Aspergillus flavus, Mucor indicus, 10 against Salmonella typhii, S. flexneri, M. gypseum, 11 against K. pneumonia, M. gypseum, 12 against K. pneumonia, and M. gypseum show superior zone of inhibitions and exhibited excellent antibacterial and antifungal activities at a MIC value of 6.25 μg/mL. Moreover, all the tested compounds 7-12 revealed promising antitubercular activity against Mycobacterium tuberculosis H37Rv and INH-resistant M. tuberculosis. Compounds 8 against M. tuberculosis and 11 against INH-resistant M. tuberculosis exhibited the percentage of reduction in RLU at 89 and 85%, respectively.