Synthesis and Analysis of (g,g', g'', - Trifluoro)neopentyl (TFNP) Aryl ethers as a Polar Aliphatic Motif.

A route is developed to (g,g',g''''-trifluoro)neopentyl (TFNP) aryl ethers to extend the methods for the introduction of the tert-butyl group, carrying a fluorine on each of the methyl  substituents. The route combines neopentyltosylate 3 with phenols and thiophenols to give efficient substitution reactions to the corresponding TFNP aryl ethers. The three C-F bonds adopt a helical propeller conformation as revealed by computation and single crystal X-ray structure analysis. The LogPs of TFNP ethers are lower (more hydrophilic) than their tert-butyl analogues. The metabolism of selected TFNP ethers was explored in the fungus Cunninghamella elegans.

Biological, phytochemical and molecular docking characteristics of Laurus nobilis L. fresh leaves essential oil from Palestine.

BACKGROUND: The historical use of Laurus nobilis L., the plant is native to the Mediterranean region and has been cultivated for its aromatic leaves, which are used as a flavoring agent in cooking and for their potential therapeutic properties. METHODS: The purpose of the current investigation was to characterize the essential oil composition of the fresh L. nobilis leaves from Palestine by using the gas chromatography-mass spectrometry (GC-MS) technique. DPPH (2,2-diphenyl-1-picrylhydrazyl), p-nitrophenyl butyrate, and 3,5-dinitro salicylic acid (DNSA) methods were employed to estimate the antioxidant, antiobesity, and antidiabetic effects of the essential oil. While MTS assay were used to evaluate their antiproliferative activities on panels of cell lines. Moreover, the docking studies were aided by the Prime MM GBSA method for estimating binding affinities. RESULTS: The GC-MS investigation demonstrated that the fresh L. nobilis leaves essential oil has a variety of chemicals, about 31 different biochemicals were identified, and the major compounds were 1,8-cineole (48.54 ± 0.91%), terpinyl acetate (13.46 ± 0.34%), and α-terpinyl (3.84 ± 0.35%). Furthermore, the investigated oil demonstrated broad-spectrum antimicrobial activity against all tested bacterial and candidal strains and significantly inhibited the growth of MCF-7 cancerous cells more than the chemotherapeutic drug Doxorubicin. Furthermore, it contains robust DPPH free radicals, as well as porcine pancreatic α-amylase and lipase enzymes. Using the 1,8-cineole compound as the predominant biomolecule found in the L. nobilis essential oil, molecular docking studies were performed to confirm these observed fabulous results. The molecular docking simulations proposed that these recorded biological activities almost emanated from its high ability to form strong and effective hydrophobic interactions, this led to the getting of optimal fitting and interaction patterns within the binding sites of the applied crystallographic protein targets. CONCLUSION: The results of these experiments showed that the fresh L. nobilis leaves essential oil has outstanding pharmacological capabilities, making this oil a potential source of natural medications.

Chemical composition, anticancer, antimicrobial activity of Aloysia citriodora Palau essential oils from four different locations in Palestine.

The primary aim of this investigation was to determine the anticancer and antimicrobial properties of essential oils (EOs) extracted from the leaves of Aloysia citriodora Palau, which were procured from four separate locations in Palestine, in addition to analyzing their chemical composition. These areas include Jericho, which has the distinction of being the lowest location on Earth, at 260 m below sea level. The EOs were acquired by hydrodistillation, and their chemical composition was examined utilizing gas chromatography-mass spectrometry (GC-MS). The minimum inhibitory concentration (MIC) of EOs was assessed against six bacterial strains and one fungal species using 96-well microtiter plates. The primary components found in these oils are geranial (26.32-37.22%), neral (18.38-29.00%), and α-curcumene (7.76-16.91%) in three regions. α-Curcumene (26.94%), spathulenol (13.69%), geranial (10.79%), caryophyllene oxide (8.66%), and neral (7.59%) were found to be the most common of the 32 chemical components in the EO from Jericho. The EOs exhibited bactericidal properties, particularly against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), and showed highly effective fungicidal activity. Nevertheless, the antifungal efficacy of the EO was found to surpass its antibacterial activity when administered at lower dosages. The EOs exhibited anticancer activities against melanoma cancer cells, as indicated by their IC50 values, which ranged from 4.65 to 7.96 µg/mL. A. citriodora EO possesses substantial antifungal and anticancer characteristics, rendering it appropriate for utilization in food-related contexts, hence potentially enhancing the sustainability of the food sector.

Exploring the phytoconstituents, antimicrobial potency, and cytotoxic effects of essential oil from Origanum punonense from Palestine.

BACKGROUND: Origanum punonense Danin is one of the old traditional medicinal plants Bedouins utilize in the Dead Sea region to treat a variety of illnesses, those caused by infections. The current study aimed to identify the phytochemical components of O. punonense essential oil (EO) and determine its antiproliferative and antimicrobial effects. METHODS: Gas chromatography and mass spectrometry were employed to detect the phytochemical constituents of O. punonense EO. Broth microdilution assay was utilized to determine the antimicrobial effects against various microbial species, including those causing diabetic foot infections. RESULTS: This study revealed that O. punonense EO contains 44 phytochemical compounds, of which 41 compounds were detectable and amounted to 99.78% of the total oil. The main chemical components of the oil were carvacrol (57.4%), p-cymene (6.66%), carvone (5.35%), pinene (4.9%), and terpinene (2.96%). The antiproliferative activity of different concentrations of O. punonense EO was noted in all of the investigated cell lines, with the best activity at the concentration of 500 µg/mL. The greatest antibacterial activity was against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Proteus vulgaris, with MIC values of 1.56 µL/mL. In addition, and the O. punonense EO showed strong antifungal activity against Candida albicans with a MIC value of 0.8 µL/mL. In addition, the O. punonense EO showed potent antibacterial activity against all MRSA samples obtained from the diabetic foot with a MIC value of 3.13 µL/mL. The O. punonense EO demonstrated potent activity against Carbapenem-resistant Enterobacterales, Citrobacter freundii, and K. pneumoniae, with MICs value of 6.25 µL/mL. CONCLUSION: The potent antiproliferative and broad antimicrobial activity of O. punonense EO makes it an effective strategy for treating infections, especially in immunocompromised patients with chronic comorbidities such as cancer and diabetes mellitus.

Eucalyptus camaldulensis Dehnh Leaf Essential Oil from Palestine Exhibits Antimicrobial and Antioxidant Activity but No Effect on Porcine Pancreatic Lipase and α-Amylase.

Eucalyptus camaldulensis Dehnh is a tree species that is commonly used for various purposes, including forestry, agroforestry, and conservation. The present investigation was designed to determine the composition of E. camaldulensis leaves essential oil and estimate its free radicals, porcine pancreatic lipase, α-amylase inhibitory, and antimicrobial properties in vitro. The chemical constituents were analyzed using the gas chromatography-mass spectrometry (GC-MS) technique. DPPH (2,2-diphenyl-1-picrylhydrazyl), p-nitrophenyl butyrate, and 3,5-dinitro salicylic acid (DNSA) methods were employed to estimate the antioxidant, antiobesity, and antidiabetic effects of the essential oil. The microdilution assay was employed to assess the antimicrobial efficacy of the substance against a total of seven distinct microbial species. The GC-MS results revealed that E. camaldulensis essential oil contains 52 components that makeup 100% of the entire oil. The main chemical constituents in E. camaldulensis essential oil are p-cymene (38.64%), followed by aromadendrene (29.65%), and 1,8-cineol (6.45%), with monocyclic monoterpene being the most abundant phytochemical group, followed by the sesquiterpene hydrocarbon group, representing 44.27 and 31.46%, respectively. The essential oil showed a weak antioxidant effect and had no antilipase or antiamylase effects. At the same time, the oil showed a strong antimicrobial effect against methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, and Proteus vulgaris, which was even more potent than the positive controls, ciprofloxacin and ampicillin, which had MIC doses of 0.2 ± 0.01, 0.2 ± 0.01, and 6.25 ± 0.1 µg/mL, respectively. It also has a strong anti-Candida albicans effect with a MIC of 0.2 ± 0.01 µg/mL. In light of these findings, in vivo studies should be conducted to determine the efficiency of the E. camaldulensis essential oil in treating microbial infections.

Silver-Catalyzed Cascade Radical Bicyclization Reaction: An Atom- and Step-Economical Strategy Accessing γ-Lactam Containing Isoquinolinediones.

An efficient and convenient method for the cascade radical bicyclization of N-phenyl-4-pentenamides with N-methyl-N-methacryloylbenzamides under silver-catalyzed conditions is described. Based on this newly developed strategy, a variety of valuable γ-lactam containing isoquinolinediones can be effectively synthesized in one step within 0.5 h, during which two C-C bonds, one C-N bond, and two new N-heterocycles were formed concurrently. With N-aryl allyl carbamates, similar 2-oxazolidinone substituted isoquinolinedione compounds can likewise be produced. The approach demonstrates wide functional group compatibility, high step- and atom-economy, and the ability to be scaled up to gram quantities in a satisfactory yield. It marks the first instance of introducing γ-lactams into isoquinoline-1,3(2H,4H)-diones to construct linked hybrid drug-like molecules, thereby making this strategy highly attractive to drug discovery.

Electrophysiological Assessment of Newly Synthesized 2,3-Benzodiazepine Derivatives for Inhibiting the AMPA Receptor Channel.

Three major subtypes of ionotropic receptors regulate glutamatergic synaptic transmission, one of which is α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPARs). They are tetrameric, cation-permeable ionotropic glutamate receptors found across the brain. Abnormalities in AMPA receptor trafficking and synaptic assembly are linked to cognitive decline and neurological diseases such as Alzheimer's, Parkinson's, and Huntington's. The present study will investigate the effects of four novel 2,3-benzodiazepine derivatives on AMPA receptor subunits by comparing their effects on synaptic responses, desensitization, and deactivation rate in human embryonic kidney cells (HEK293T) recombinant AMPAR subunits using whole-cell patch-clamp electrophysiology. All four 2,3-BDZ compounds showed inhibitory activity against all the homomeric and heteromeric subunits tested. While the desensitization and deactivation rates in 2,3-BDZ-1 and 2,3-BDZ-2 decreased and increased, respectively, in the other two compounds (i.e., 2,3-BDZ-3 and 2,3-BDZ-4), there was no change in the desensitization or deactivation rates. These results contribute to a better understanding of AMPARs by identifying potential 2,3-BDZ drugs that demonstrate inhibitory effects on the AMPAR subunits.

The effect of Lavandula Coronopifolia essential oil on the biophysical properties of desensitization and deactivation gating currents in ionotropic receptors.

The rising incidence of cancer and the lack of effective therapeutic interventions for many neurological illnesses like Alzheimer's and epilepsy has prompted us to investigate the composition and effects of the Lavandula coronopifolia oil from Palestine on cancer cells and AMPA receptor subunits in the brain due to the vast range of beneficial properties of Lavandula coronopifolia essential oil (EO). GC/MS was used to analyze L. coronopifolia's EO chemistry. EO's cytotoxicity and biophysical effects on AMPA receptors were investigated using MTS and electrophysiological techniques. The GC-MS results revealed that L. coronopifolia EO has a high content of eucalyptol (77.23%), ß-pinene (6.93%), and α-pinene (4.95%). The EO showed more significant antiproliferative selectivity activities against HepG2 cancer cell lines than HEK293T cell lines with IC50 values of 58.51 and 133.22 µg/mL, respectively. The EO of L. coronopifolia affected AMPA receptor kinetics (desensitization and deactivation) and preferred homomeric GluA1 and heteromeric GluA1/A2 receptors. These findings indicate the potential therapeutic use of L. coronopifolia EO in the selective treatment of HepG2 cancer cell lines and neurodegenerative diseases.

Chemical Markers and Pharmacological Characters of Pelargonium graveolens Essential Oil from Palestine.

Pelargonium graveolens leaves are widely used in traditional medicine for relieving some cardiovascular, dental, gastrointestinal, and respiratory disorders. They are also used as food and tea additives in Palestine and many other countries. Consequently, this investigation aimed to describe the chemical markers, cytotoxic, antioxidant, antimicrobial, metabolic, and cyclooxygenase (COX) enzymes inhibitory characteristics of P. graveolens essential oil (PGEO) from Palestine utilizing reference methods. There were 70 chemicals found in the GCMS analysis, and oxygenated terpenoids were the most abundant group of the total PGEO. Citronellol (24.44%), citronellyl formate (15.63%), γ-eudesmol (7.60%), and iso-menthone (7.66%) were the dominant chemical markers. The EO displayed strong antioxidant activity (IC50 = 3.88 ± 0.45 µg/mL) and weak lipase and α-amylase suppressant effects. Notably, the PGEO displayed high α-glucosidase inhibitory efficacy compared with Acarbose, with IC50 doses of 52.44 ± 0.29 and 37.15 ± 0.33 µg/mL, respectively. PGEO remarkably repressed the growth of methicillin-resistant Staphylococcus aureus (MRSA), even more than Ampicillin and Ciprofloxacin, and strongly inhibited Candida albicans compared with Fluconazole. The highest cytotoxic effect of the PGEO was noticed against MCF-7, followed by Hep3B and HeLa cancer cells, with IC50 doses of 32.71 ± 1.25, 40.71 ± 1.89, and 315.19 ± 20.5 µg/mL, respectively, compared with doxorubicin. Moreover, the screened EO demonstrated selective inhibitory activity against COX-1 (IC50 = 14.03 µg/mL). Additionally, PGEO showed a weak suppressant effect on COX-2 (IC50 = 275.97 µg/mL). The current research can be considered the most comprehensive investigation of the chemical and pharmacological characterization of the PGEO. The results obtained in this study demonstrate, without doubt, that this plant represents a rich source of bioactive substances that can be further investigated and authenticated for their medicinal potential.

Isolation, Identification and Pharmacological Effects of Mandragora autumnalis Fruit Flavonoids Fraction.

Since ancient times, Mandragora autumnalis has been used as a traditional medicinal plant for the treatment of numerous ailments. In light of this, the current study was designed to isolate and identify the chemical constituents of the flavonoids fraction from M. autumnalis ripe fruit (FFM), and evaluate its DPPH scavenging, anti-lipase, cytotoxicity, antimicrobial and antidiabetic effects. An ethyl acetate extract of M. autumnalis was subjected to a sequence of silica gel column chromatography using different eluents with various polarities. The chemical structures of the isolated compounds were identified using different spectral techniques, including 1H NMR and 13C NMR. FFM's anti-diabetic activity was assessed using a glucose transporter-4 (GLUT4) translocation assay, as well as an inhibition against α-amylase and α-glucosidase using standard biochemical assays. The FFM anti-lipase effect against porcine pancreatic lipase was also evaluated. Moreover, FFM free radical scavenging activity using the DPPH test and antimicrobial properties against eight microbial strains using the micro-dilution method were also assessed. Four flavonoid aglycones were separated from FFM and their chemical structures were identified. The structures of the isolated compounds were established as kaempferol 1, luteolin 2, myricetin 3 and (+)-taxifolin 4, based on NMR spectroscopic analyses. The cytotoxicity test results showed high cell viability (at least 90%) for up to 1 mg/mL concentration of FFM, which is considered to be safe. A dose-dependent increase in GLUT4 translocation was significantly shown (p < 0.05) when the muscle cells were treated with FFM up to 0.5 mg/mL. Moreover, FFM revealed potent α-amylase, α-glucosidase, DPPH scavenging and porcine pancreatic lipase inhibitory activities compared with the positive controls, with IC50 values of 72.44 ± 0.89, 39.81 ± 0.74, 5.37 ± 0.41 and 39.81 ± 1.23 µg/mL, respectively. In addition, FFM inhibited the growth of all of the tested bacterial and fungal strains and showed the greatest antibacterial activity against the K. pneumoniae strain with a MIC value of 0.135 µg/mL. The four flavonoid molecules that constitute the FFM have been shown to have medicinal promise. Further in vivo testing and formulation design are needed to corroborate these findings, which are integral to the pharmaceutical and food supplement industries.

Constituents, Antibacterial Adhesion, Cytotoxic and in Vitro Metastasis Blocking Properties of Salvia fruticosa Essential Oils from Three Palestinian Localities.

Essential oils (EOs) of Salvia fruticosa Mill. gathered from three Palestinian localities were studied to determine their constituents, antibacterial adhesion impact against Klebsiella pneumonia, cytotoxicity, and their function in cancer cell migration. Gas chromatography-mass spectrometry identified the chemical components, while the MTT technique was used to measure the EOs' cytotoxicity against HeLa (cervical) and Caco-2 (colorectal) cancer cells. Antibacterial adhesion was assessed by examining Klebsiella pneumoniae's ability to adhere to Caco-2 cells. Our study found that eucalyptol was present as the main constituent in all S. fruticosa EOs. In addition, K. pneumoniae adhesion and metastasis were reduced after 48 h of application. Salfit's and Hebron's EOs had the most potent cytotoxic effects on Caco-2 and HeLa, with IC50 values in the range of 0.7-1.3 µg/mL. Taking into account the obtained results, it may be concluded that S. fruticosa EOs can serve as potential disinfectant agents for the treatment and prevention of K. pneumoniae-associated illness and cancer.

Isolation, identification, and antimycotic activity of plumbagin from Plumbago europaea L. roots, leaves and stems.

Plumbago europaea L. is a plant utilized in Palestinian ethnomedicine for the treatment of various dermatological diseases. The current investigation was designed to isolate plumbagin from P. europaea leaves, roots and for the first time from the stems. Moreover, it aimed to evaluate the antimycotic activity against three human fungal pathogens causing dermatophytosis, also against an animal fungal pathogen. The qualitative analysis of plumbagin from the leaves, stems, and roots was conducted using HPLC and spectrophotometer techniques, while the structure of plumbagin was established utilizing Proton and Carbon-13 Nuclear Magnetic Resonance (NMR) and Infrared (IR) techniques. The entire plant constituents were determined by GC-MS. Moreover, the antimycotic activity against Ascosphaera apis, Microsporum canis, Trichophyton rubrum, and Trichophyton mentagrophytes was assessed utilizing the poison food technique method. The percentage of plumbagin recorded in the leaves, stems, and roots was found to be 0.51±0.001%, 0.16±0.001%, and 1.65±0.015%, respectively. The GC-MS examination declared the presence of 59 molecules in the plant extract. The plant extract and pure plumbagin exhibited complete inhibition against all tested dermatophytes at 6.0mg/mL for the extracts and 0.2mg/mL for plumbagin. P. europaea root is the best source of plumbagin and the plant extract could represent a potential drug candidate for the treatment of dermatophytosis infections. Further studies required to design suitable dosage forms from the natural P. europaea root extracts or plumbagin alone, to be utilized for the treatment of dermatological and veterinary ailments.

Phytochemical Profile, Antimicrobial, Cytotoxic, and Antioxidant Activities of Fresh and Air-Dried Satureja nabateorum Essential Oils.

Satureja nabateorum (Danin and Hedge) Bräuchler is a perennial herb in the Lamiaceae family that was discovered and classified in 1998. This green herb is restricted to the mountains overlooking the Dead Sea, specifically in Jordan's southwest, the Edom mountains, and the Tubas mountains in Palestine. Gas chromatography-mass spectrometry (GC-MS) analysis of essential oil (EO) of air-dried and fresh S. nabateorum resulted in the identification of 30 and 42 phytochemicals accounting for 99.56 and 98.64% of the EO, respectively. Thymol (46.07 ± 1.1 and 40.64 ± 1.21%) was the major compound, followed by its biosynthetic precursors γ-terpinene (21.15 ± 1.05% and 20.65 ± 1.12%), and p-cymene (15.02 ± 1.02% and 11.51 ± 0.97%), respectively. Microdilution assay was used to evaluate the antimicrobial property of EOs against Staphylococcus aureus (ATCC 25923), clinical isolate Methicillin-Resistant Staphylococcus aureus (MRSA), Enterococcus faecium (ATCC 700221) Klebsiella pneumoniae (ATCC 13883), Proteus vulgaris (ATCC 700221), Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 27853) and Candida albicans (ATCC-90028). With a MIC of 0.135 µg/mL, the EOs has the most potent antibacterial action against K. pneumonia. Both EOs display good antifungal efficacy against C. albicans, with a MIC value of 0.75 µg/mL, which was better than that of Fluconazole's (positive control, MIC = 1.56 µg/mL). The antioxidant capacity of EOs extracted from air-dried and fresh S. nabateorum was determined using the DPPH assay, with IC50 values of 4.78 ± 0.41 and 5.37 ± 0.40 µg/mL, respectively. The tested EOs showed significant cytotoxicity against Hela, HepG2, and COLO-205 cells, with IC50 values ranging from 82 ± 0.98 to 256 ± 1.95 µg/mL. The current work shows there is a possibility to use the S. nabateorum EOs for various applications.

Glechoma curviflora Volatile Oil from Palestine: Chemical Composition and Neuroprotective, Antimicrobial, and Cyclooxygenase Inhibitory Activities.

The rise of the emergence of microbial resistance of antibiotics, the dangerous side effects of nonsteroidal anti-inflammatory drugs, and noncompetent medications of Alzheimer's, Parkinson's, and other neurodegenerative diseases prompt scientists to search for phytochemicals that could be utilized in the remedy of lethal diseases. Glechoma curviflora (Boiss.) Kuntze (Nepeta curviflora) is a medicinal herb growing in the eastern parts of the Mediterranean Sea Basin and is widely consumed as a tea. The leaves of this plant have been traditionally used for the treatment of various infectious diseases. The current research was designed to identify the chemical composition of Glechoma curviflora (Boiss.) essential oil (EO) and to assess its antibacterial, antifungal, and cyclooxygenase inhibitory activities and the biophysical gating effect on AMPA receptors. Twenty phytochemicals were identified from G. curviflora leaves and flowers EO amounting to almost 100% of the total constituents using GC-MS technique, of which 1,6-dimethylspiro[4.5]decane (27.51%) 1, caryophyllene oxide (20.08%) 2, and ß-caryophyllene (18.28%) 3 were the main constituents. The biophysical properties' effect from the plant extract on various AMPA-type receptors expressed in Human Embryonic Kidney (HEK293) cells was assessed by exploiting the whole-cell patch-clamp technique. Microdilution assay was adopted for assessing the antimicrobial property against eight virulent microbial strains whilst the cyclooxygenase inhibition effect was accomplished utilizing COX inhibitory screening colorimetric assay G. curviflora EO displayed potent activity against P. aeruginosa (MIC = 1.25 µg/mL), S. sonnei (MIC = 3.12 µg/mL), and E. coli (MIC = 1.25 µg/mL), compared with ciprofloxacin (positive control) and potent antibacterial activity against S. aureus, MRSA, S. sonnei, E. coli, and P. aeruginosa compared to Ampicillin (2nd positive control). It also showed anti-Candida (MIC = 6.25 µg/mL) and antimold (MIC = 3.125 µg/mL) activities compared with fluconazole (antifungal positive control). Likewise, our results showed an inhibition and biophysical impact of G. curviflora on all AMPARs subunits.

Fluorine-Induced Pseudo-Anomeric Effects in Methoxycyclohexanes through Electrostatic 1,3-Diaxial Interactions.

We report counter-intuitive axial preferences in non-stereochemically biased, selectively fluorinated methoxycyclohexanes. These pseudo-anomeric effects are apparent when electronegative CF2 groups are placed at the C-2, C-4 and C-6 positions of the cyclohexane ring to render the C-3/5 axial hydrogen atoms electropositive. The electrostatic interaction between these axial hydrogen atoms and the -OMe oxygen is stabilising. The effect is explored using high-level ab initio and DFT calculations in the framework of NBO, QTAIM and NCI analysis across a range of derivatives, and experimentally (19 F{1 H}-NMR at -80 °C) for some illustrative examples. The effect is significant in energy terms for a weak interaction, and illustrates a new stereoelectronic aspect attributed to selective fluorine substitution in organic chemistry.

Synthesis of organic liquid crystals containing selectively fluorinated cyclopropanes.

This paper describes the synthesis of a series of organic liquid crystals (LCs) containing selectively fluorinated cyclopropanes at their termini. The syntheses used difluorocarbene additions to olefin precursors, an approach which proved straightforward such that these liquid crystal candidates could be efficiently prepared. Their physical and thermodynamic properties were evaluated and depending on individual structures, they either displayed positive or negative dielectric anisotropy. The study gives some guidance into effective structure-property relationships for the design of LCs containing selectively fluorinated cyclopropane motifs.

Probing the helical integrity of multivicinal all-syn-fluoro alkanes.

This study extends our interest in the synthesis and conformational behaviour of all-syn multivicinal fluoro alkane motifs. Specifically an all-syn 1,2,3,6,7,8-hexafluorooctane chain was assembled with a run of three fluorines, of the same stereochemical sense (syn) to the direction of the chain, on each side of an ethylene (-CH2CH2-) spacer to explore if the helical sense of the chain crosses the ethylene bridge. The solid state (X-ray) structure indicated a continuous helix however in solution (NMR) and by DFT computation, although the individual all-syn 1,2,3-trifluoro motifs maintain good helical integrity, the molecule is much more dynamic across the ethylene bridge. It was notable however that a low energy, non-helical conformer has a high molecular dipole (µ = 7.15 D) indicating a role for this skipped motif in soft materials such as liquid crystals or polar polymers.

Fingerprinting, Antimicrobial, Antioxidant, Anticancer, Cyclooxygenase and Metabolic Enzymes Inhibitory Characteristic Evaluations of Stachys viticina Boiss. Essential Oil.

The present study aimed to identify the chemical constituents and to assess the in-vitro, antimicrobial, anticancer, antioxidant, metabolic enzymes and cyclooxygenase (COX) inhibitory properties of essential oil (EO) of Stachys viticina Boiss. leaves. The S. viticina EO was isolated and identified using microwave-ultrasonic and GC-MS techniques, respectively. Fifty-two compounds were identified, of which endo-borneol was the major component, followed by eucalyptol and epizonarene. The EO was evaluated against a panel of in-vitro bioassays. The EO displayed antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli and Epidermophyton floccosum, with MIC values of 0.039, 0.078 and 0.78 mg/mL, respectively. The EO exhibited cytotoxicity against HeLa (cervical adenocarcinoma) and Colo-205 (colon) cancer cell lines with percentages of inhibition of 95% and 90%, for EO concentrations of 1.25 and 0.5 mg/mL, respectively. Furthermore, it showed metabolic enzyme (α-amylase, α-glucosidase, and lipase) inhibitory (IC50 = 45.22 ± 1.1, 63.09 ± 0.26, 501.18 ± 0.38 µg/mL, respectively) and antioxidant activity, with an IC50 value of 19.95 ± 2.08 µg/mL. Moreover, the S. viticina EO showed high cyclooxygenase inhibitory activity against COX-1 and COX-2 with IC50 values of 0.25 and 0.5 µg/mL, respectively, similar to those of the positive control (the NSAID etodolac). Outcomes amassed from this investigation illustrate that S. viticina EO represents a rich source of pharmacologically active molecules which can be further validated and explored clinically for its therapeutic potential and for the development and design of new natural therapeutic preparations.

Fluorine-containing substituents: metabolism of the α,α-difluoroethyl thioether motif.

We report the metabolism of the recently introduced α,α-difluoroethyl thioether motif to explore further its potential as a substituent for bioactives discovery chemistry. Incubation of two aryl-SCF2CH3 ethers with the model yeast organism Cunninghamella elegans, indicates that the sulfur of the thioether is rapidly converted to the corresponding sulfoxide, and then significantly more slowly to the sulfone. When the substrate was (p-OMe)PhSCF2CH3, then the resultant (demethylated) phenol sulfoxide had an enantiomeric excess of 60%, and when the substrate was the ß-substituted-SCF2CH3 naphthalene, then the enantiomeric excess of the resultant sulfoxide was 54%. There was no evidence of defluorination, unlike the corresponding oxygen ether (p-OMe)PhOCF2CH3, which was converted to the (demethylated) phenol acetate ester during C. elegans incubation. We conclude that the aryl-S-CF2CH3 motif is metabolised in a similar manner to aryl-SCF3, a motif that is being widely explored in discovery chemistry. It is however, significantly less lipophilic than aryl-SCF3 which may offer a practical advantage in tuning overall pharmacokinetic profiles of molecules in development.

Isolation of naturally occurring novel isoflavonoids: an update.

Covering: Jan. 2012 to Dec. 2017 This review describes the 391 new isoflavonoids isolated and identified from natural sources between January 2012 and December 2017, commenting on their sources, identification and biological activities. Due to the length of this review, the synthesis of isoflavonoids is not included. Furthermore, new applications of analytical techniques for the isolation and identification of isoflavonoids are also reviewed.