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A study of cofacially arrayed π-systems is of particular importance for the design of functional materials for efficient long-range intra-chain charge transfer through the bulk semiconducting materials in the layers of photovoltaic devices. The effect of π-stacking between a pair of aromatic rings has been mainly studied in the form of cyclophanes, where aromatic rings are forced into a sandwich-like geometry, which extensively deforms the aromatic rings from planarity. The synthetic difficulties associated with the preparation of cyclophane-like structures has prevented the synthesis of many examples of their multi-layered analogues. Moreover, the few available multi-layered cyclophanes are not readily amenable to the structural modification required for the construction of D–spacer–A triads needed to explore mechanisms of electron and energy transfer. In this review, we recount how a detailed experimental and computational analysis of 1,3-diarylalkanes led to the design of a new class of cofacially arrayed polyfluorenes that retain their π-stacked structure. Thus, efficient synthetic strategies have been established for the ready preparation of monodisperse polyfluorenes with up to six π-stacked fluorenes, which afford ready access to D–spacer–A triads by linking donor and acceptor groups to the polyfluorene spacers via single methylenes. Detailed 1H NMR spectroscopy, X-ray crystallography, electrochemistry, and He(I) photoelectron spectroscopy of F2–F6 have confirmed the rigid cofacial stacking of multiple fluorenes in F2–F6, despite the presence of rotatable C–C bonds. These polyfluorenes (F2–F6) form stable cation radicals in which a single hole is delocalized amongst the stacked fluorenes, as judged by the presence of intense charge-resonance transition in their optical spectra. Interestingly, these studies also discern that delocalization of a single cationic charge could occur over multiple fluorene rings in F2–F6, while the exciton is likely localized only onto two fluorenes in F2–F6. Facile synthesis of the D–spacer–A triads allowed us to demonstrate that efficient triplet energy transfer can occur through π-stacked polyfluorenes; the mechanism of energy transfer crosses over from tunneling to hopping with increasing number of fluorenes in the polyfluorene spacer. We suggest that the development of rigidly held π-stacked polyfluorenes, described herein, with well-defined redox and optoelectronic properties provides an ideal scaffold for the study of electron and energy transfer in D-spacer-A triads, where the Fn spacers serve as models for cofacially stacked π-systems.

Phytochemical investigation of chloroform fraction (DBC) and ethyl acetate fraction (DBE) of D. bupleuroides (Acanthaceae) resulted in the isolation of β-sitosterol (1) from DBC and vanillic acid (2) from DBE, which were first to be isolated from D. bupleuroides. β-Sitosterol (1) exhibited substantial antioxidant activity (IC50 = 198.87 µg/mL), whereas vanillic acid (2) showed significant antioxidant power (IC50 = 92.68 µg/mL) employing 1,1-diphenyl-2-picrylhydrazyl (DPPH*) radical scavenging capacity assay. Both compounds showed pronounced antimicrobial activity using the agar disc diffusion method, particularly against fungi showing MIC values of 0.182 and 0.02 concerning Candida albicans, respectively, and 0.001 mg/mL regarding Penicillium notatum. They revealed considerable antibacterial activity with MIC values ranging between 0.467 and 0.809 mg/mL. Vanillic acid (2) exhibited substantial anticancer potential displaying 48.67% cell viability at a concentration of 100 μg/mL using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-Diphenyl-2H-Tetrazolium Bromide) assay concerning HepG2 cell lines. These results were further consolidated by in silico studies on different enzymes, where vanillic acid displayed a high fitting score in the active pockets of DNA-gyrase, dihydrofolate reductase, aminoglycoside nucleotidyltransferase, and β-lactamase. It also inhibited human cyclin-dependent kinase 2 (CDK-2) and DNA topoisomerase II, as revealed by the in silico studies. ADME/TOPKAT (absorption, distribution, metabolism, excretion, and toxicity) prediction showed that vanillic acid exhibited reasonable pharmacodynamic, pharmacokinetic, and toxicity properties and, thus, could perfectly together with D. bupleuroides crude extract be incorporated in pharmaceutical preparations to counteract cancer and microbial invasion, as well as oxidative stress. Thus, it is concluded that D. bupleroides could be a potential source of therapeutically active compounds, which would be helpful for the discovery of clinically effective and safe drugs.

A new triterpene glycoside, silviridoside, was isolated from the aerial parts of Silene viridiflora (Caryophyllaceae) using different chromatographic techniques. The structure of silviridoside was comprehensively elucidated as 3-O-β-D-galacturonopyranosyl-quillaic acid 28-O-β-D-glucopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→3)]-β-D-fucopyranosyl ester by one- and two-dimensional nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HR-MS). Silviridoside showed promising antioxidant activity in different antioxidant assays such as 2,2-diphenyl-1-picrylhydrazyl (DPPH) (2.32 mg TE/g), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) (1.24 mg TE/g), cupric-reducing antioxidant capacity (CUPRAC) (9.59 mg TE/g), ferric-reducing antioxidant power (FRAP) (5.13 mg TE/g), phosphomolybdenum (PHD) (0.28 mmol TE/g), and metal-chelating (MCA) (6.62 mg EDTA/g) assays. It exhibited a good inhibitory potential on acetylcholinesterase (AChE) (2.52 mg GALAE/g), butyrylcholinesterase (BChE) (7.16 mg GALAE/g), α-amylase (0.19 mmol ACAE/g), α-glucosidase (1.21 mmol ACAE/g), and tyrosinase (38.83 mg KAE/g). An in silico evaluation of the pharmacodynamic, pharmacokinetic, and toxicity properties of silviridoside showed that the new compound exhibited reasonable pharmacodynamic and pharmacokinetic properties without any mutagenic effect, but slight toxicity. Thus, it could be concluded that silviridoside could act as a promising lead drug for pharmaceutical and nutraceutical developments to combat oxidative stress and various disorders, but a future optimization is necessary.

Pimenta racemosa is a commonly known spice used in traditional medicine to treat several ailments. In this study, comprehensive phytochemical profiling of the essential oils and methanol extracts of P. racemosa leaves and stems was performed, alongside assessing their potential Helicobacter pylori inhibitory activity in vitro and in silico. The essential oils were chemically profiled via GC-MS. Moreover, the methanol extracts were profiled using HPLC-PDA-ESI-MS/MS. The antibacterial activity of the essential oils and methanol extracts against H. pylori was determined by adopting the micro-well dilution method. GC-MS analysis unveiled the presence of 21 constituents, where eugenol represented the major component (57.84%) and (59.76%) in both leaves and stems of essential oils, respectively. A total of 61 compounds were annotated in both leaves and stems of P. racemosa methanolic extracts displaying richness in phenolic compounds identified as (epi)catechin and (epi)gallocatechin monomers and proanthocyanidins, hydrolyzable tannin derivatives (gallotannins), flavonoids, and phenolic acids. The stem essential oil showed the most promising inhibitory effects on H. pylori, exhibiting an MIC value of 3.9 µg/mL, comparable to clarithromycin with an MIC value of 1.95 µg/mL. Additionally, in silico molecular modeling studies revealed that decanal, eugenol, terpineol, delta-cadinene, and amyl vinyl showed potential inhibitory activity on H. pylori urease as demonstrated by high-fitting scores indicating good binding to the active sites. These findings indicate that P. racemosa comprises valuable phytochemical constituents with promising therapeutic effects, particularly the stem, an economic agro-industrial waste.

Periodontitis, as one of the most common diseases on a global scale, is a public health concern. Microbial resistance to currently available antimicrobial agents is becoming a growing issue in periodontal treatment. As a result, it is critical to develop effective and environmentally friendly biomedical approaches to overcome such challenges. The investigation of Streptomyces rochei MS-37’s performance may be the first of its kind as a novel marine actinobacterium for the green biosynthesis of silver nanoparticles (SNPs) and potentials as antibacterial, anti-inflammatory, antibiofilm, and antioxidant candidates suppressing membrane-associated dental infections. Streptomyces rochei MS-37, a new marine actinobacterial strain, was used in this study for the biosynthesis of silver nanoparticles for various biomedical applications. Surface plasmon resonance spectroscopy showed a peak at 429 nm for the SNPs. The SNPs were spherical, tiny (average 23.2 nm by TEM, 59.4 nm by DLS), very stable (−26 mV), and contained capping agents. The minimum inhibitory concentrations of the SNPs that showed potential antibacterial action ranged from 8 to 128 µg/mL. Periodontal pathogens were used to perform qualitative evaluations of microbial adhesion and bacterial penetration through guided tissue regeneration membranes. The findings suggested that the presence of the SNPs could aid in the suppression of membrane-associated infection. Furthermore, when the anti-inflammatory action of the SNPs was tested using nitric oxide radical scavenging capacity and protein denaturation inhibition, it was discovered that the SNPs were extremely efficient at scavenging nitric oxide free radicals and had a strong anti-denaturation impact. The SNPs were found to be more cytotoxic to CAL27 than to human peripheral blood mononuclear cells (PBMCs), with IC50 values of 81.16 µg/mL in PBMCs and 34.03 µg/mL in CAL27. This study’s findings open a new avenue for using marine actinobacteria for silver nanoparticle biosynthesis, which holds great promise for a variety of biomedical applications, in particular periodontal treatment.

In this study, a series of coumarin derivatives, either alone or as hybrids with cinnamic acid, were synthesized and evaluated for their cytotoxicity against a panel of cancer cells using the MTT assay. Then, the most active compounds were inspected for their mechanism of cytotoxicity by cell-cycle analysis, RT-PCR, DNA fragmentation, and Western blotting techniques. Cytotoxic results showed that compound (4) had a significant cytotoxic effect against HL60 cells (IC50 = 8.09 µM), while compound (8b) had a noticeable activity against HepG2 cells (IC50 = 13.14 µM). Compounds (4) and (8b) mediated their cytotoxicity via PI3K/AKT pathway inhibition. These results were assured by molecular docking studies. These results support further exploratory research focusing on the therapeutic activity of coumarin derivatives as cytotoxic agents.

There has been a lot of interest in the manufacture of stable, high-efficiency photocatalysts. In this study, initially Cr doped ZnFe2O4 nanoparticles (NPs) were made via surfactant-assisted hydrothermal technique. Then Cr-ZnFe2O4 NPs were modified by incorporating S-g-C3N4 to enhance their photocatalytic efficiency. The morphological, structural, and bonding aspects were analyzed by XRD, FTIR, and SEM techniques. The photocatalytic efficiency of the functional Cr-ZnFe2O4/S-g-C3N4 (ZFG) heterostructure photocatalysts was examined against MB under sunlight. The produced ZFG-50 composite has the best photocatalytic performance, which is 2.4 and 3.5 times better than that of ZnFe2O4 and S-g-C3N4, respectively. Experiments revealed that the enhanced photocatalytic activity of the ZFG nanocomposite was caused by a more effective transfer and separation of photo-induced charges. The ZFG photocatalyst can use sunlight for treating polluted water, and the proposed modification of ZnFe2O4 using Cr and S-g-C3N4 is efficient, affordable, and environmentally benign. Under visible light, Gram-positive and Gram-negative bacteria were employed to ZFG-50 NCs’ antimicrobial activity. These ZFG-50 NCs also exhibit excellent antibacterial potential.

Herein, 2,3-dioxo-1,2,3,4-tetrahydroquinoxaline was used as a bio-isosteric scaffold to the phthalazinone motif of the standard drug Olaparib to design and synthesize new derivatives of potential PARP-1 inhibitory activity using the 6-sulfonohydrazide analog 3 as the key intermediate. Although the new compounds represented the PARP-1 suppression impact of IC50 values in the nanomolar range, compounds 8a, 5 were the most promising suppressors, producing IC50 values of 2.31 and 3.05 nM compared to Olaparib with IC50 of 4.40 nM. Compounds 4, 10b, and 11b showed a mild decrease in the potency of the IC50 range of 6.35–8.73 nM. Furthermore, compounds 4, 5, 8a, 10b, and 11b were evaluated as in vitro antiproliferative agents against the mutant BRCA1 (MDA-MB-436, breast cancer) compared to Olaparib as a positive control. Compound 5 exhibited the most significant potency of IC50; 2.57 µM, whereas the IC50 value of Olaparib was 8.90 µM. In addition, the examined derivatives displayed a promising safety profile against the normal WI-38 cell line. Cell cycle, apoptosis, and autophagy analyses were carried out in the MDA-MB-436 cell line for compound 5, which exhibited cell growth arrest at the G2/M phase, in addition to induction of programmed apoptosis and an increase in the autophagic process. Molecular docking of the compounds 4, 5, 8a, 10b, and 11b into the active site of PARP-1 was carried out to determine their modes of interaction. In addition, an in silico ADMET study was performed. The results evidenced that compound 5 could serve as a new framework for discovering new potent anticancer agents targeting the PARP-1 enzyme.

Medicinal plants are widely used in folk medicine to treat various diseases. Thonningia sanguinea Vahl is widespread in African traditional medicine, and exhibits antioxidant, antibacterial, antiviral, and anticancer activities. T. sanguinea is a source of phytomedicinal agents that have previously been isolated and structurally elucidated. Herein, gas chromatography combined with tandem mass spectrometry (GC-MS/MS) was used to quantify epipinoresinol, β-sitosterol, eriodictyol, betulinic acid, and secoisolariciresinol contents in the methanolic crude extract and its ethyl acetate fraction for the first time. The ethyl acetate fraction was rich in epipinoresinol, eriodictyol, and secoisolariciresinol at concentrations of 2.3, 3.9, and 2.4 mg/g of dry extract, respectively. The binding interactions of these compounds with the epidermal growth factor receptor (EGFR) were computed using a molecular docking study. The results revealed that the highest binding affinities for the EGFR signaling pathway were attributed to eriodictyol and secoisolariciresinol, with good binding energies of −19.93 and −16.63 Kcal/mol, respectively. These compounds formed good interactions with the key amino acid Met 769 as the co-crystallized ligand. So, the ethyl acetate fraction of T. sanguinea is a promising adjuvant therapy in cancer treatments.

Voriconazole (VRC) is a broad-spectrum antifungal agent belonging to BCS class II (biopharmaceutical classification system). Despite many efforts to enhance its solubility, this primary issue still remains challenging for formulation scientists. Transethosomes (TELs) are one of the potential innovative nano-carriers for improving the solubility and permeation of poorly soluble and permeable drugs. We herein report voriconazole-loaded transethosomes (VRCT) fabricated by the cold method and followed by their incorporation into carbopol 940 as a gel. The prepared VRCT were evaluated for % yield, % entrapment efficiency (EE), surface morphology, possible chemical interaction, particle size, zeta potential, and polydispersity index (PDI). The optimized formulation had a particle size of 228.2 nm, a zeta potential of −26.5 mV, and a PDI of 0.45 with enhanced % EE. Rheology, spreadability, extrudability, in vitro release, skin permeation, molecular docking, antifungal, and antileishmanial activity were also assessed for VRCT and VRC loaded transethosomal gel (VTEG). Ex-vivo permeation using rat skin depicted a transdermal flux of 22.8 µg/cm2/h with enhanced efficiency up to 4-fold. A two-fold reduction in inhibitory as well as fungicidal concentration was observed against various fungal strains by VRCT and VTEG besides similar results against L-donovani. The development of transethosomal formulation can serve as an efficient drug delivery system through a topical route with enhanced efficacy and better patient compliance.

In this study isolates from Thymelaea hirsuta, a wild plant from the Sinai Peninsula of Egypt, were identified and their selective cytotoxicity levels were evaluated. Phytochemical examination of the ethyl acetate (EtOAc) fraction of the methanolic (MeOH) extract of the plant led to the isolation of a new triflavanone compound (1), in addition to the isolation of nine previously reported compounds. These included five dicoumarinyl ethers found in Thymelaea: daphnoretin methyl ether (2), rutamontine (3), neodaphnoretin (4), acetyldaphnoretin (5), and edgeworthin (6), two flavonoids: genkwanin (7) and trans-tiliroside (8), p-hydroxy benzoic acid (9) and β sitosterol glucoside (10). Eight of the isolated compounds were tested for in vitro cytotoxicity against Vero and HepG2 cell lines using a sulforhodamine-B (SRB) assay. Compounds 1, 2 and 5 exhibited remarkable cytotoxic activities against HepG2 cells, with IC50 values of 8.6, 12.3 and 9.4 μM, respectively, yet these compounds exhibited non-toxic activities against the Vero cells. Additionally, compound 1 further exhibited promising cytotoxic activity against both MCF-7 and HCT-116 cells, with IC50 values of 4.26 and 9.6 μM, respectively. Compound 1 significantly stimulated apoptotic breast cancer cell death, resulting in a 14.97-fold increase and arresting 40.57% of the cell population at the Pre-G1 stage of the cell cycle. Finally, its apoptosis-inducing activity was further validated through activation of BAX and caspase-9, and inhibition of BCL2 levels. In silico molecular docking experiments revealed a good binding mode profile of the isolates towards Ras activation/pathway mitogen-activated protein kinase (Ras/MAPK), a common molecular pathway in the development and progression of liver tumors.

The genus Cotula (Asteraceae) comprises about 80 species, amongst them Cotula anthemoides L. It is a wild plant growing in Egypt that possesses many traditional uses as a headache, colic, and chest cold remedy. In our study, the chemical composition of C. anthemoides essential oils was analyzed using GC-MS spectroscopy. Sixteen components of leave and stem oils and thirteen components of flower oils were characterized. The main components in both essential oil parts were camphor (88.79% and 86.45%) and trans-thujone (5.14% and 10.40%) in the leaves and stems and the flowers, respectively. The anti-inflammatory activity of the oils in lipopolysaccharide-stimulated RAW 264.7 macrophage cells was evaluated. The flower oil showed its predominant effect in the amelioration of proinflammatory cytokines and tumor necrosis factor-α, as well as cyclooxygenase-2. The bornyl acetate showed the highest affinity for the cyclooxygenase-2 receptor, while compound cis-p-menth-2-ene-1-ol had the best affinity for the tumor necrosis factor receptor, according to the results of molecular docking. In addition, the molecule cis-β-farnesene showed promising dual affinity for both studied receptors. Our findings show that essential oils from C. anthemoides have anti-inflammatory properties through their control over the generation of inflammatory mediators. These findings suggest that C. anthemoides essential oils could lead to the discovery of novel sources of anti-inflammatory treatments.

Candida is the most common fungal class, causing both superficial and invasive diseases in humans. Although Candida albicans is the most common cause of fungal infections in humans, C. auris is a new emergent serious pathogen causing complications similar to those of C. albicans. Both C. albicans and C. auris are associated with high mortality rates, mainly because of their multidrug-resistance patterns against most available antifungal drugs. Although several compounds were designed against C. albicans, very few or none were tested on C. auris. Therefore, it is urgent to develop novel effective antifungal drugs that can accommodate not only C. albicans, but also other Candida spp., particularly newly emergent one, including C. auris. Inspired by the significant broad-spectrum antifungal activities of the essential oil cuminaldehyde and the reported wide incorporation of azoles in the antifungal drugs, a series of compounds (UoST1-11) was designed and developed. The new compounds were designed to overcome the toxicity of the aldehyde group of cuminaldehyde and benefit from the antifungal selectivity of azoles. The new developed UoST compounds showed significant anti-Candida activities against both Candida species. The best candidate compound, UoST5, was further formulated into polymeric nanoparticles (NPs). The new formula, UoST5-NPs, showed similar activities to the nanoparticles-free drug, while providing only 25% release after 24 h, maintainng prolonged activity up to 48 h and affording no toxicity. In conclusion, new azole formulations with significantly enhanced activities against C. albicans and C. auris, while maintaining prolonged action and no toxicities at lower concentrations, were developed.

Glycerol and aminophenol intermolecular condensation has been investigated through a milling and microwave-assisted sequential strategy, towards the synthesis of a benzoxaxine derivative. Mechanochemical activation prior to the microwave-assisted process could improve the probability of contact between the reagents, and greatly favors the higher conversion of aminophenol. At the same time, following a mechanochemical–microwave sequential approach could tune the selectivity towards the formation of a benzoxazine derivative, which could find application in a wide range of biomedical areas.

Background: Hepatocellular carcinoma (HCC) is one of the most widespread malignancies and is reported as the fourth most prevalent cause of cancer deaths worldwide. Therefore, we aimed to investigate the probable mechanistic cytotoxic effect of the promising 2-thioxoimidazolidin-4-one derivative on liver cancer cells using in vitro and in vivo approaches. The compounds were tested for the in vitro cytotoxic activity using MTT assay, and the promising compound was tested in colony forming unit assay, flow cytometric analysis, RT-PCR, Western blotting, in vivo using SEC-carcinoma and in silico to highlight the virtual mechanism of action. Both compounds 4 and 2 performed cytotoxic effects against HepG2 cells with IC50 values of 0.017 and 0.18 μM, respectively, compared to Staurosporine and 5-Fu as reference drugs with IC50 values of 5.07 and 5.18 µM, respectively. Compound 4 treatment revealed apoptosis induction by 19.35-fold (11.42% compared to 0.59% in control), arresting the cell cycle at G2/M phase. Moreover, studying gene expression that plays critical roles in cell cycle and apoptosis by RT-PCR demonstrated that compound 4 enhances the expression of the pro-apoptotic genes p53, PUMA, and Caspase 3, 8, and 9, and impedes the anti-apoptotic Bcl-2 gene in the HepG2 cells. It can also inhibit the PI3K/AKT pathway at both gene and protein levels, which was reinforced by the in silico predictions of the molecular docking simulations towards the PI3K/AKT proteins. Finally, in vivo study verified that compound 4 has a promising anti-cancer activity through activating antioxidant levels (CAT, SOD and GSH) and ameliorating hematological, biochemical, and histopathological findings.