Endophytic fungi, particularly from higher plants have proven to be a rich source of antimicrobial secondary metabolites. The purpose of this study is to examine the antimicrobial potential of three endophytic fungi Aspergillus sp. SA1, Aspergillus sp. SA2, and Aspergillus sp. SA3, cultivated from Nigella sativa seeds against Staphylococcus aureus (ATCC 9144), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), Klebsiella pneumoniae (ATCC 13883), MRSA (ATCC 33591), and human pathogen Candida albicans (ATCC 10231). Furthermore, the most active cultivated endophytic fungi were molecularly identified via internal transcribed spacer (ITS) sequencing. HR-ESIMS guided approach has been used successfully in chemical profiling of 26 known bioactive secondary metabolites (1–26), which belongs to different classes of natural compounds such as polyketides, benzenoids, quinones, alcohols, phenols or alkaloids. Finally, in-silico interactions within active site of fungal Cyp51 and bacterial DNA gyrase revealed possibility of being a hit-target for such metabolites as antimicrobials.

New 5-aminosalicylamide-4-thiazolinone hybrids (27) were efficiently synthesized, characterized, and evaluated to explore their structure–activity relationship as anticancer agents. The antiproliferative activities of the new hybrids were evaluated against eight cancer cell lines using the sulforhodamine B assay. The most potent compound (24b) possessed high selectivity on the tested cell lines in the low micromolar range, with much lower effects on normal fibroblast cells (IC₅₀ > 50 µM). The cell lines derived from leukemia (Jurkat), cervix (HeLa), and colon (HCT116) cancers appeared to be the most sensitive, with IC₅₀ of 2 µM. 24b is the N-ethylamide derivative with p-dimethylaminobenzylidene at position 5 of the 4-thiazolinone moiety. Other N-substituents or arylidene derivatives showed lower activity. Hybrids with salicylamides showed lower activity than with methyl salicylate. The results clearly show that the modifications of the carboxy group and arylidene moiety greatly affect the activity. Investigating the possible molecular mechanisms of these hybrids revealed that they act through cell-cycle arrest and induction of apoptosis and epidermal growth factor receptor (EGFR) inhibition. Molecular docking studies rationalize the molecular interactions of 24b with EGFR. This work expands our knowledge of the structural requirements to improve the anticancer activity of 5-aminosalicylic-thiazolinone hybrids and pave the way toward multitarget anticancer salicylates.

Narcissus plants have long been recognized as a source of natural cosmetics and skincare botanicals since ancient times. Among them, Narcissus pseudonarcissus L. was commonly used for a plethora of skin disorders, e.g. abscesses, sores, burns, bruising, freckles, and wounds; however, no previous scientific reports have deliberated its wound curative properties. Therefore, this study was designed to explore the wound healing potential of the total extract of N. pseudonarcissus bulbs and its derived fractions (I‒IV) on normal lung fibroblast (WI-38) cells using the wound scratch assay. Firstly, the possible cytotoxic effects of N. pseudonarcissus total ethanol extract and fractions towards WI-38 cells were examined using the MTT assay and the most appropriate concentrations (either non-toxic or showing the least toxicity) were selected for the wound healing assay accordingly. Overall, WI-38 cells treated with 31.25 and 62.50 μg/mL of the petroleum ether fraction (I) exhibited both negligible cytotoxicity (IC₅₀= 1207.96 μg/mL) and the highest wound closure and migration rates after 24 and 48 h compared to either the untreated control cells as well as those treated with the other fractions. Additionally, phytochemical analysis of fraction (I) led to the isolation of varied metabolites, e.g. hydrocarbons, monoglycerides, pyrrolidines, and steroids that were first described herein in either the genus Narcissus or the family Amaryllidaceae. Finally, molecular docking analysis of the identified metabolites revealed their possible interaction with a group of enzymes that affect different stages of wound healing, particularly steroidal metabolites, of which sitosterol 3-O-β-glucopyranoside-6ꞌ-O-hexadecanoate (7) showed noteworthy binding affinities to TGF-β, GSK-3, TNF-α, and IL-1β proteins. These findings could therefore endorse the traditional use of N. pseudonarcissus for wounds and its potential to develop alternative plant-derived cosmeceuticals for skin repair.

The crude extract and its derived ethyl acetate fraction of the soft coral Nephthea mollis displayed remarkable in vitro antitrypanosomal activity against Trypanosoma brucei with IC50 values of 6.4 and 3.7 μg/ml, respectively. Consequently, the crude extract was subjected to LC–HR–ESI–MS metabolomics profiling to identify the constituents that may underlie their bioactivities. As a result, 33 secondary metabolites were characterized, among which sesquiterpenes and diterpenes prevailed. In silico molecular modeling revealed the high binding affinity for the ornithine decarboxylase active site, with five dereplicated compounds having docking scores higher than the cocrystallized ligand. These results highlight N. mollis as a rich source of compounds that might help develop therapies for Human African trypanosomiasis.

A new series inspired by combining fragments from nitazoxanide (NTZ) and 4-aminosalicylic acid (4-ASA) was synthesized and screened for in vitro antibacterial and antimycobacterial activities. The majority showed higher antibacterial potency than NTZ against all the screened strains, notably, 5f, 5j, 5n and 5o with MICs of 0.87–9.00 μM. Compounds 5c, 5n and 5o revealed higher potency than ciprofloxacin against K. pneumoniae, while 5i was equipotent. For E. faecalis, 3b, 5j, and 5k showed higher potency than ciprofloxacin. 5j was more potent against P. aeruginosa than ciprofloxacin, while 5n was more potent against S. aureus with an MIC of 0.87 μM. 5f showed equipotency to ciprofloxacin against H. pylori with an MIC of 1.74 μM. Compounds 3a and 3b (4-azidoNTZ, MIC 4.47 μM) are 2 and 5-fold more potent against Mycobacterium tuberculosis (Mtb H₃₇Rv) than NTZ (MIC 20.23 μM) and safer. 4-Azidation and/or acetylation of NTZ improve both activities, while introducing 1,2,3-triazoles improves the antibacterial activity. Molecular docking studies within pyruvate ferredoxin oxidoreductase (PFOR), glucosamine-6-phosphate synthase (G6PS) and dihydrofolate reductase (DHFR) active sites were performed to explore the possible molecular mechanisms of actions. Acceptable drug-likeness properties were found. This study may shed light on further rational design of substituted NTZ as broad-spectrum more potent antimicrobial candidates.

After COVID-19 pandemic, Mucormycosis (black fungus) spreads as one of its related complications, due to the decrease in immunity system after administration of COVID-19 treatment drugs. A combination therapy of Itraconazole (ITR) and Terbinafine (TEB) was proved to be effective for treatment of black fungus. A novel electrochemical sensor was designed for estimation of ITR & TEB simultaneously by square wave voltammetric (SWV) technique. The sensor was fabricated using N&S-codoped magnetic quantum dots (N,S-MQDs) and ruthenium nanoparticles (Ru NPs). The fabricated sensor was characterized by cyclic voltammetry (CV), scanning electron microscope (SEM), powder X ray diffraction (pXRD), Fourier transform-Infrared (FT-IR), Raman spectroscopy and electrochemical impedance spectroscopy (EIS). Full optimization study for various experimental and instrumental parameters, in addition to method validation following International conference on Harmonization (ICH) guidelines was achieved. A good linearity in the range of 0.5–30 μg mL− 1 with limit of detection (LOD) 0.24 and 0.19 μg mL− 1 for ITR and TEB, respectively were obtained. The sensor was applied for analysis of ITR and TEB simultaneously in human plasma and urine samples without any interferences by applying dispersive magnetic solid phase micro-extraction (dMSPE) technique, where excellent recovery results exceeding 95 % were achieved

The endemicity of the pandemic coronavirus disease 2019 (COVID‐19) infection proved to be transitional only. Spikes are forming again in 2023, and high expectations are returning for reinfections and viral mutations. Molnupiravir (MOL) has been approved as an oral antiviral drug for the treatment of the COVID‐19 causative virion. Therefore, the development of an ultrasensitive, instantaneous, and cost‐effective method for the quantification of MOL in real plasma samples and formulated dosage form are mandatory. The proposed approach is based on the synthesis of a MOL metal‐chelation product. MOL as a ligand was chelated with 1.0 mM zinc(II) in an acetate buffer (pH 5.3). After illumination at 340 nm, the intensity of the MOL fluorescence measured at 386 nm was increased by about 10‐fold. The linearity range was found to be from 60.0 to 800.0 ng mL−1 with limit of quantitation (LOQ) of 28.6 ng mL−1 . Two methods were utilized for measuring the greenness of the proposed method (Green Analytical Procedure Index [GAPI] and analytical greenness metric [AGREE] methods), with results equal to 0.8. The binding stoichiometry of MOL with the zinc(II) ion was found to be 2:1. All the experimental parameters were optimized and validated using International Conference on Harmonization (ICH) and United States Food and Drug Administration (US‐ FDA) recommendations. Furthermore, the fluorescent probes were successfully utilized in real human plasma with high percentages of recovery (95.6%–97.1%) without any matrix interferences. The mechanism of fluorescent complex formation was confirmed using 1 H NMR in the presence and absence of Zn(II). The method was further utilized for testing content uniformity of MOL in its marketed capsule dosage forms