Organic and Medicinal Chemistry Letters最新文献

Background: The aim of the current investigation was to identify bioactive secondary metabolites including phenols, tannins, flavonoids, terpinedes, and steroids and compare the phytochemical analysis and antioxidant profile of the juice extracted from the fruits of Citrus sinensis, Citrus anrantifolia, and Citrus limonum.

Results: Phytochemical screening is important for the isolation of new, novel, and rare secondary metabolites before bulk extraction. Phytochemical analysis of the desired plant fruits of family Rutaceae revealed the presence of phenols, flavonoids, reducing sugars, steroids, terpinedes and tannins. The fruits of C. sinensis and C. anrantifolia exhibited the presence of phenols, flavonoids, reducing sugars, steroids, terpinedes and tannins, while the fruits of C. limonum indicated the presence of phenols, flavonoids, reducing sugars, terpinedes, and tannins. The fruits of selected plants were also subjected to antioxidant potential by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay against ascorbic acid at various concentrations. Among the tested plants, C. sinensis showed promising antiradical effect (84.81%) which was followed by C. Anrantifolia (80.05%) at 100 μg/ml against ascorbic acid (96.36%). The C. limonum showed low antioxidant activity among the three selected plants of family Rutaceae.

Conclusions: The current finding is baseline information in the use of the fruits of selected plants as food supplement which may be due to the presence of antioxidant molecules in the family Rutaceae. Further research is needed in this area to isolate the phenolic constituents which possess ideal antiradical potential.

Background: Phenylazonaphtol-β-D-O-glycosides are alternative substrates for the detection of enzymatic activity of β-glycosidases which are involved in various important processes. These azoic compounds are currently exploited as prodrugs for colonic disease due the presence of β-glycosidase activity in the gut flora and therefore allowing the release of the drug at the specific site.

Results: Phenylazonaphtol-β-D-O-glucoside 3a and galactoside 3b were prepared via diazonium salt conditions under weak acidic conditions which do not compromise the O-glycosidic bond stability, by coupling reaction between 2-naphtol sodium salt with aminoglycosides 1a and 1b. The resulting phenylazonaphtol glycosides 2a and 2b were deprotected affording the phenylazonaphtol glycosides 3a and 3b in quantitative yield. The galactoside glycoside 3b was assayed as substrate for in vitro β-galactosidase enzymatic activity showing strong absorbance after releasing of the azoic chromophore. Also, docking studies were performed to determine the best pose as well as the interactions between the ligand and the residues located at the active site.

Conclusions: The methodology developed for synthesizing the phenylazonaphtol glycosides described proved to be convenient for generating azoic functionalities in the presence of glycosidic bonds and the glycosides suitable as alternative substrates and potentially useful prodrugs in the treatment of colonic diseases.

Background: Schiff's bases are excellent ligands which are synthesized from the condensation of primary amines with carbonyl groups.

Findings: The classical reaction for the synthesis of Schiff's bases in an ethanolic solution and glacial acetic acid as a catalyst was followed in the synthesis of substituted sulfamethoxazole compounds.

Conclusions: Some Schiff's bases containing sulfamethoxazole nucleus have been synthesized and characterized. The present compounds are hoped to be applied in the photostability of PVC.

Background: The level of expression of cannabinoid receptor type 2 (CB2R) in healthy and diseased brain has not been fully elucidated. Therefore, there is a growing interest to assess the regional expression of CB2R in the brain. Positron emission tomography (PET) is an imaging technique, which allows quantitative monitoring of very low amounts of radiolabelled compounds in living organisms at high temporal and spatial resolution and, thus, has been widely used as a diagnostic tool in nuclear medicine. Here, we report on the radiofluorination of N-aryl-oxadiazolyl-propionamides at two different positions in the lead structure and on the biological evaluation of the potential of the two tracers [18F]1 and [18F]2 as CB2 receptor PET imaging agents.

Results: High binding affinity and specificity towards CB2 receptors of the lead structure remained unaffected by the structural changes such as the insertion of the aliphatic and aromatic fluorine in the selected labelling sites of 1 and 2. Aliphatic and aromatic radiofluorinations were optimized, and [18F]1 and [18F]2 were achieved in radiochemical yields of ≥30% with radiochemical purities of ≥98% and specific activities of 250 to 450 GBq/μmol. Organ distribution studies in female CD1 mice revealed that both radiotracers cross the blood-brain barrier (BBB) but undergo strong peripheral metabolism. At 30 min after injection, unmetabolized [18F]1 and [18F]2 accounted for 60% and 2% as well as 68% and 88% of the total activity in the plasma and brain, respectively. The main radiometabolite of [18F]2 could be identified as the free acid [18F]10, which has no affinity towards the CB1 and CB2 receptors but can cross the BBB.

Conclusions: N-aryl-oxadiazolyl-propionamides can successfully be radiolabelled with 18F at different positions. Fluorine substitution at these positions did not affect affinity and specificity towards CB2R. Despite a promising in vitro behavior, a rather rapid peripheral metabolism of [18F]1 and [18F]2 in mice and the generation of brain permeable radiometabolites hamper the application of these radiotracers in vivo. However, it is expected that future synthetic modification aiming at a replacement of metabolically susceptible structural elements of [18F]1 and [18F]2 will help to elucidate the potential of this class of compounds for CB2R PET studies.

Background: Drug metabolism and pharmacokinetic (DMPK) assessment has come to occupy a place of interest during the early stages of drug discovery today. Computer-based methods are slowly gaining ground in this area and are often used as initial tools to eliminate compounds likely to present uninteresting pharmacokinetic profiles and unacceptable levels of toxicity from the list of potential drug candidates, hence cutting down the cost of the discovery of a drug.

Results: In the present study, we present an in silico assessment of the DMPK profile of our recently published natural products database of 1,859 unique compounds derived from 224 species of medicinal plants from the Cameroonian forest. In this analysis, we have used 46 computed physico-chemical properties or molecular descriptors to predict the absorption, distribution, metabolism and elimination (ADME) of the compounds. This survey demonstrated that about 50% of the compounds within the Cameroonian medicinal plant and natural products (CamMedNP) database are compliant, having properties which fall within the range of ADME properties of >95% of currently known drugs, while >73% of the compounds have ≤2 violations. Moreover, about 72% of the compounds within the corresponding 'drug-like' subset showed compliance.

Conclusions: In addition to the previously verified levels of 'drug-likeness' and the diversity and the wide range of measured biological activities, the compounds in the CamMedNP database show interesting DMPK profiles and, hence, could represent an important starting point for hit/lead discovery from medicinal plants in Africa.

Background: Pyrazole and pyrazolone motifs are well known for their wide range of biological activities such as antimicrobial, anti-inflammatory, and antitumor activities. The incorporation of more than one pharmacophore in a single scaffold is a well known approach for the development of more potent drugs. In the present investigation, a series of differently substituted 4-arylidene pyrazole derivatives bearing pyrazole and pyrazolone pharmacophores in a single scaffold was synthesized.

Results: The synthesis of novel 4-arylidene pyrazole compounds is achieved through Knovenagel condensation between 1,3-diaryl-4-formylpyrazoles and 3-methyl-1-phenyl-1H-pyrazol-5-(4H)-ones in good yields. All compounds were evaluated for their in vitro antimicrobial activity.

Conclusions: A series of 4-arylidene pyrazole derivatives was evaluated for their in vitro antimicrobial activity against two Gram-positive (Bacillus subtilis and Staphylococcus aureus) and two Gram-negative bacteria (Pseudomonas fluorescens and Escherichia coli), as well as two pathogenic fungal strains (Candida albicans and Saccharomyces cerevisiae). The majority of the compounds displayed excellent antimicrobial profile against the Gram-positive (B. subtilis and S. aureus), and some of them are even more potent than the reference drug ciprofloxacin.