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An efficient and eco-friendly approach for synthesizing difluoromethyl- and aryldifluoromethyl-substituted polycyclic imidazoles was established via a visible-light-promoted radical cyclization reaction. This method employed the readily accessible and inexpensive CF2HCO2H or PhCF2COOH, along with benzimidazoles bearing unactivated alkenes and PhI(OAc)2 as substrates, and proceeded without the need of any base, metal catalyst, photocatalyst or additive. In total, 24 examples were examined, and all of them successfully underwent cyclization reaction to produce the target products in good to excellent yields. Mechanistic studies revealed that the reaction proceeds via a radical pathway.

Abstract Background Exploring the therapeutic potential of unutilized plant parts from agricultural crops represents a promising strategy for discovering novel medications with high positive economic value. This study aimed to characterize the composition, antidiabetic, anti-obesity, antioxidant, and cytotoxic effects of volatile oil (VO) extracted from the leaves of Citrus japonica trees. This is the first research to assess the C. japonica VO’s anti-obesity, anti-lipase, and cytotoxic properties. Using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assays and gas chromatography–mass spectrometry (GC–MS) analysis, the components of VO and its capacity to suppress the growth of cancer and other abnormal cells were ascertained, respectively. Stable 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals, p-nitrophenyl butyrate (PNPB), and dinitrosalicylic acid (DNSA) assays were employed to determine antioxidant, anti-obesity, and antidiabetic activities, respectively. Results The C. japonica leaf showed significant diversity in type and percentage of VO molecules. Overall, 45 compounds were identified in the VO, constituting 99.69% of the total oil composition. γ-Muurolene (28.12%), β-eudesmol (10.93%), γ-eudesmol (8.44%), germacrene B (7.39%), and elemol (7.27%) are the major characterized molecules. According to the inhibition percentage results of DPPH free radicals, porcine pancreatic lipase, and α-amylase, the VO exhibits strong antioxidant properties and weak inhibitory effects on lipase and α-amylase enzymes. The C. japonica VO showed a moderate cytotoxic effect against Hep3B and considerable activity on B16F1, CaCo-2, HeLa, MCF-7, and HepG2, with IC50 doses in the range of 69.7–171.96 µg/mL. The VO cytotoxic effect IC50 against the normal cell line LX-2 was 224.95 µg/mL. Conclusion The current study collectively presented the chemical constituents of C. japonica leaf VO from Palestine for the first time and demonstrated its inhibitory effects against DPPH free radicals, porcine pancreatic lipase, and α-amylase. The results suggest that C. japonica leaf VO has the potential to be used as a natural supplement to prevent or treat cancer, as well as in the food industry as a natural antioxidant. Graphical Abstract

Abstract Background The complex composition of essential oils (EOs) derived from plants offers potential therapeutic approaches for treating various medical conditions, including neurological disorders and infectious diseases. This research aimed to comprehensively analyze the phytochemical composition of Iris haynei EO and evaluate its pharmacological properties, specifically its cytotoxicity, antimicrobial activity, and modulation of AMPA receptors. Results The analysis of I. haynei EO, conducted using gas chromatography and mass spectroscopy, identified diethyl phthalate, α-terpineol, and benzyl acetate as the main components. Cytotoxicity experiments on several cancer cell lines revealed a dose-dependent impact. Electrophysiological recordings on HEK293T cells expressing AMPARs showed varying levels of inhibition across different subunits, with receptors encoding GluA2 exhibiting the most significant effects. The EO also demonstrated significant antibacterial activity against both Gram-positive and Gram-negative bacteria, as well as fungi. Conclusions The findings of this study underscore the potential therapeutic benefits of I. haynei EO, particularly in treating neurological conditions associated with AMPA receptor dysfunction and exhibiting antimicrobial activity against infectious agents. The promising results warrant further investigation into the pharmacological effects of the EO, suggesting a novel approach for addressing cerebral ischemia and related neurological diseases. Graphical Abstract

Abstract 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.

Abstract 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.

Abstract 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.

Abstract Background Fennel (Fe), also known scientifically as Foeniculum vulgare, and Micromeria fruticose are herbaceous plants endemic to the Mediterranean Region. The use of their essential oils for their health-promoting effects has been seen in Middle-Eastern societies, where they have been used as a type of traditional medicine. These oils have been used to treat a variety of diseases, including headaches, abdominal pains, skin and eye infections, colds, and wounds. This study looks at the chemical makeup of essential oils extracted from Palestine-grown fennel seeds and Micromeria fruticose leaves. The anticancer properties of each essential oil, as well as the combined mixture of both oils, were evaluated against the melanoma cell line. Results GC–MS was used to study the essential oils (EOs) from Micromeria fruticose leaves and fennel seeds that were extracted by hydrodistillation. Analysis of M. fruticose EO allowed the identification of 20 compounds, accounting for 97.73% of the EO's overall composition, with pulegone (81.77%), β-caryophyllene (2.95%), isomenthone (2.17%), piperitenone oxide (1.78%), and p-mentha-3-en-8-ol (1.38%) being the primary components. 24 phytochemicals were identified in the essential oil of fennel seeds, accounting for 100% of its composition, of which trans-anethole (93.69%), fenchone (3.93%), and sylvestrene (0.83%) were the major constituents. Although the EOs derived from M. fruticosa leaves and fennel seeds have shown potential for inhibiting the growth of several types of cancer, their impact on the proliferation and migration of melanoma cells has not been investigated. The results of our study demonstrate that the application of both oils, either separately or in combination (referred to as Mix-EO therapy), effectively suppressed the growth of melanoma cells in a manner that was dependent on the dosage. Furthermore, both treatments resulted in the upregulation of pro-apoptotic Bax and the downregulation of apoptosis-inhibiting Bcl2 expression in an in vitro setting. The anti-proliferative effects were confirmed using a murine melanoma model in vivo. Furthermore, both the individual EOs that were assessed and their combination (Mix-EO) exhibited inhibitory properties against the migration of melanoma cells. Both EOs and Mix-EO were found to decrease the intracellular levels of the transcription factor nuclear factor kappa B (NFkB) and one of its downstream targets, matrix metalloproteinase9 (MMP9), in melanoma and tumor-associated mesenchymal stem cells. Finally, we demonstrate for the first time that EOs from M. fruticose leaves, fennel seeds, and their combination exert anti-cancer characteristics by inhibiting NFkB and MMP9 in melanoma (autocrine) and tumor-associated mesenchymal stem (paracrine) cells, thereby inducing melanoma cell apoptosis and preventing cell migration. Conclusions The findings of our investigation indicate that the EOs derived from the fennel seeds and the M. fruticose leaves encompass a diverse array of biologically active chemicals, which have robust anticancer effects. The results of this study hold promise for application in the advancement of innovative natural medications. Additional investigation is required to delve into the medicinal capacity of these essential oils in biological entities. Graphical Abstract

Abstract Background Over the past decade, researchers have been exploring the potential therapeutic benefits of volatile oils (VOs) in addressing various disorders, particularly those associated with an increase in fungal infections. This study aimed to analyze the chemical compositions of three different thyme species growing in Palestine using gas chromatography–mass spectroscopy (GC–MS) and explore their antifungal characteristics. The thyme species investigated in this research encompass Origanum syriacum L., Clinopodium serpyllifolium subsp. fruticosum (L.) Bräuchler, and Thymbra capitata (L.) Cav. Methods The VOs of the investigated plants were extracted by hydrodistillation technique equipped with Cleavenger apparatus and characterized by utilizing GC–MS equipment. Moreover, the extracted VOs were evaluated for their antifungal activity using the broth microdilution assay against several clinically isolated Candida species and one ATCC strain. Results The GC–MS characterization results of O. syriacum VO revealed the presence of 22 components and the abundant molecules were thymol (37.36%), carvacrol (27.71%), γ-terpinene (17.47%), and p-cymene (7.80%), while 19 compounds were characterized in the C. serpyllifolium VO and the major components were p-cymene (37.58%), carvacrol (22.93%), and γ-terpinene (21.91%). In addition, 23 compounds were identified in T. capitata VO and the main components were carvone (59.45%), pulegone (21.59%), menthone (4.24%), and isomenthone (3.71%). According to the antifungal assay results, VO extracted from O. syriacum has the highest activity among all the screened VOs. Conclusion All the VOs screened in this study exhibit promising antifungal activities for various potential medical applications. Consequently, we strongly advocate for further biological investigations of these oils in the near future. Graphical Abstract

Abstract Background Myrtus communis L. leaves, due to their tonic and antiseptic properties, have been used as folk medicine in many communities to treat a variety of conditions such as inflammation, peptic ulcers, diarrhea, leucorrhoea, headaches, excessive perspiration, and skin diseases. In this study, we examined the chemical makeup and biological properties of M. communis essential oils (EOs) from two locations in Palestine, including Jericho, the world's deepest site and Jenin. The plant's methanol and ethyl acetate extracts' biological efficacy were also assessed. Results The GC–MS analysis revealed that the EO of M. communis leaves from Jenin included 39 components, the majority were 1,8-cineole (31.98%), linalool (21.94%), linalool acetate (11.42%), α-pinene (10.22%), and myrtenol (6.87%). While 33 compounds, were discovered in M. communis EO from Jericho, with cis-4-thujanol (27.37%), 1,8-cineole (24.32%), myrtenol (12.97%), and myrtenal (12.46%) being the main constituents. The EO, ethyl acetate, and methanol extracts were tested (in vitro) for antibacterial, anticancer, antioxidant, and α-amylase inhibitory properties. The EO from Jericho demonstrated greater antibacterial efficacy against Escherichia coli, Proteus vulgaris, Klebsiella pneumoniae, Staphylococcus aureus, and, methicillin-resistant Staphylococcus aureus (MRSA) with MIC values of 0.27, 0.135, 0.135, 0.27, and 0.135 mg/mL, respectively. MRSA, S. aureus and C. albicans were all susceptible to the antimicrobial efficiency of methanol and ethyl acetate extracts (MIC = 0.097–0.195, 0.097–0.195, and 0.049 mg/mL, respectively). Methanol and ethyl acetate extracts, in contrast to EOs, showed high DPPH activity, with IC50 values ranging from 3.60 ± 0.35 to 25.70 ± 0.48 µg/mL. Both oils showed moderate cytotoxic activity against HeLa, MCF7, 3T3, and LX-2 cell lines, with IC50 values ranging from 202.02 ± 2.27 to 592.40 ± 2.55 µg/mL for Jenin and 199.80 ± 3.41 to 914.54 ± 3.05 µg/mL for EO from Jericho. Furthermore, EO and methanol extracts from Jenin inhibited α-amylase with IC50 values of 950.48 ± 2.54 and 795.43 ± 1.88 µg/mL, respectively. Conclusions Our findings indicate that M. communis extracts and EOs contain a vast array of pharmacologically active compounds with potent antioxidant, antibacterial, and antifungal activities that can be exploited to develop new types of natural pharmaceuticals and warrant further in vivo investigation for their therapeutic potential. Graphical Abstract

Abstract 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%), β-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.

Abstract Laurus nobilis (LN) has been used throughout the years as a food flavoring and in traditional medicine. The LN leaves have various biological activities, such as antioxidant, wound healing, antibacterial, analgesic, and anti-inflammatory activities. However, oxidative stress, cancer, diabetes, microbial infections, and inflammatory diseases are closely linked. The objective of this research is to characterize Laurus nobilis (LN) aromatic oil (AO) and evaluate its antioxidant, antidiabetic, antiobesity, antimicrobial, and antimutagenic bioactivities. The AO constituents were characterized using gas chromatography–mass spectrometry (GC–MS). The antimicrobial activity was performed using a microdilution assay against six common microbial species. Free radicals, a porcine pancreatic lipase, α-amylase, and α-glucosidase inhibitory assays were conducted utilizing reference biomedical methods. The cytotoxic effect of LNAO was established on a variety of cancer and normal cell lines using the MTS assay. The anti-inflammatory activity of LNAO was evaluated using the Cayman COX activity kit. The results indicate about 99% of the total oil is composed of 36 compounds, the characterized AO metabolites showed content of many oxygenated terpenoids with 1,8-Cineole and Terpinyl acetate as a major component with a percentage of (40.39 and 15.07, respectively. The plant AO showed potent antioxidant activity (IC50 = 2.2 ± 1.38) and has moderate anti-amylase (IC50 = 60.25 ± 1.25), anti-glucosidase (IC50 = 131.82 ± 0.1), and antilipase (IC50 = 83.17 ± 0.06) activities. Moreover, LNAO showed potent antimicrobial activity against Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia , Proteus vulgaris (MICs = 1.56 µg/mL), methicillin-resistant Staphylococcus aureus (MRSA) (MIC = 3.125 µg/mL) and Candida albicans (MIC = 0.195 µg/mL). The cytotoxicity results demonstrated that at a concentration of 1 mg/mL, LNAO has potent breast cancer (MCF-7), and hepatocellular carcinoma (Hep 3B) cancer cells inhibitory activities of 98% and 95%, respectively. Importantly, we are the first to show that LNAO significantly hinders hepatocellular carcinoma spheroids’ formation capacity in a 3D model. These results show that LNAO is a promising natural source with powerful antioxidant, antidiabetic, anticancer, and antimicrobial activities that could be exploited in the future to treat a variety of diseases. Graphical Abstract

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.

Since the dawn of time, people have relied on herbal medicine to heal many ailments. Lavandula coronopifolia (LC) is an aromatic plant that has been utilized in ethnomedicine since ancient times. This investigation aimed to figure out the chemical constituents of the volatile oil (VO) of the LC herb from Palestine for the first time and determine its microbicidal, anti-inflammatory, and cytotoxic effects. The LC aerial parts VO phytochemical constituent characterizations were performed utilizing gas chromatography linked to a mass spectrometric system. While, the effects of LC-VO's ability to suppress microbial growth were established against selected bacterial and fungal strains by a broth microdilution technique. Besides, an in vitro cyclooxygenase enzyme (COX) suppressant bioassay kit was utilized to estimate the anti-inflammatory effect against bovine cyclooxygenase (COX) type 1 and 2. In addition, the colorimetric MTS test was employed to determine the cytotoxic activity against the cervical adenocarcinoma (HeLa) tumor cell line. Linalyl acetate (41.65 ± 0.91%) and linalool (41.41 ± 0.77%) were identified as major components of LC-VO, and oxygenated monoterpenoid was the dominant phytochemical class of this VO. The LC-VO demonstrated potent bactericidal and fungicidal effects, especially on methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, Proteus vulgaris, and Candida albicans (MIC = 0.33 ± 0.03, 0.63 ± 0.1, 1.25 ± 0.81, and 0.16 ± 0.06 µg/mL), respectively. Besides, LC-VO suppressed COX enzymes type-1 and −2, with an inhibition percentage at 50 µg/mL of 95.00 and 88.02 percent, respectively, in comparison with the positive control, ketoprofen non-steroidal anti-inflammatory drugs (NSAID), at the same concentration with an inhibition percentage of 96.25 and 65.02%, respectively. In addition, the LC-VO inhibited the growth of HeLa cells dose-dependently, with an IC50 dose of 0.71 ± 0.01 µg/mL. The current study demonstrates that LC-VO is a promising alternative for the healing or preventing various infectious diseases, cancer, and chronic inflammation. These results reveal that LC-VO has beneficial health benefits and has the potential to be utilized for therapeutic purposes.

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.

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.

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 β-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.

The chemical profiles of Rosmarinus officinalis L. essential oils, collected from five distinct geographical regions in Palestine, were determined using GC-MS. The major phytochemical classes of R. officinalis EOs were monoterpene hydrocarbon (24.81–78.75%) and oxygenated monoterpenoids (19.01–73.78%), with 1,8-cineole (4.81–37.83%), α-pinene (13.07–51.36%), and camphor (11.95–24.30%) being the most abundant components of the studied oils. Using the DPPH assay, the antioxidant activity of EOs revealed that EO from the Jenin region had the highest antioxidant activity, with an IC50 value of 10.23 ± 0.11 µg/mL, followed by samples from Tulkarm (IC50 = 37.15 ± 2.3 µg/mL) and Nablus (IC50= 38.9 ± 0.45 µg/mL). With MICs of 12.5, 12.5, 6.25, 6.25, and 6.25 µg/mL against MRSA, S. aureus, E. coli, K. pneumonia, and P. vulgaris, respectively, the EO extracted from the Jenin region of Palestine had the greatest antibacterial activity. Furthermore, EOs from Jenin and Nablus demonstrated stronger anti-candida action than the pharmaceutical formulation Fluconazole, with MICs of 0.781, 0.781, and 1.56 µg/mL, respectively.

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.

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.

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.

Under room temperature ultrasonic conditions, mixing the neutral 2,4,6-tri(pyridin-2-yl)-1,3,5-triazine (tptz) ligand with Ni(II) salt resulted in the preparation of a unique {[Ni(tptz)Cl(H2O)2]-[Ni(tptz)(H2O)3]}3Cl.5H2O complex with two different nickel(II) centers in a high yield. The crystal structure of {[Ni(tptz)Cl(H2O)2][Ni(tptz)(H2O)3]}3Cl.5H2O revealed the existence of distorted octahedral around both Ni(II) centers. The complex structure was further supported by FT-IR, UV-Vis., CHN-EA, TGA and EDX. The computed HSA was also performed to support the XRD interaction types. The existence of the H2O molecules in the crystal lattice was examined by FT-IR and TG/DTG measurements that proved the presence of coordinated and uncoordinated water molecules. Moreover, the thermal stability of the desired complex was evaluated at open atmosphere via TG/DTG and showed stability up to ~400 °C and multistep thermal decomposition.

This paper reports the synthesis of three amine stereoisomers 5a–c of the tetrafluorocyclohexyl ring system, as building blocks for discovery chemistry programmes. The synthesis starts from a Birch reduction of benzonitrile, followed by an in situ methyl iodide quench. The resultant 2,5-cyclohexadiene was progressed via double epoxidations and then hydrofluorination ring opening reactions. The resultant fluorohydrin moieties were then converted to different stereoisomers of the tetrafluorocyclohexyl ring system, and then reductive hydrogenation of the nitrile delivered three amine stereoisomers. It proved necessary to place a methyl group on the cyclohexane ring in order to stabilise the compound against subsequent HF elimination. The two all-cis tetrafluorocyclohexyl isomers 5a and 5b constitute facially polarized cyclohexane rings, with fluorines on the electronegative face and hydrogens on the electropositive face.

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.