New Benzoxazole Derivatives as Antiprotozoal Agents: In Silico Studies, Synthesis, and Biological Evaluation

Background. Benzoxazole derivatives have different biological activities. In pursuit of designing novel chemical entities with antiprotozoal and antimicrobial activities, benzoxazolyl aniline was utilized as a privileged scaffold of a series of (3-benzoxazole-2-yl) phenylamine derivatives, 3-benzoxazoloyl acetamide, and butyramide derivatives. Methods. These novel analogs were synthesized in straightforward simple chemistry without any quantitative chromatographic separations in reasonable yields. The biological evaluation of all target compounds as potential antimalarial, antileishmanial, antitrypanosomal, and antimicrobial agents was performed by various well-established cell-based methods. Results. Compounds 6d and 5a showed promising biological screening data. The amidation of 3-benzoxazolyl aniline 1 with the chloroacetyl functional group resulted in a good antimalarial activity and showed moderate inhibitory activities against leishmanial and trypanosomal spp. Moreover, chloroacetyl functionalization of benzoxazolyl aniline serves as a good early goal for constructing and synthesizing new antimicrobial and antiprotozoal agents. The molecular docking study rationalizes the relative inhibitory activity of compound 5a as an antimalarial agent with the deregulation of PfPNP activity which has emerged as a major mechanism of these targets

Synthesis, antimicrobial evaluation and docking studies of new pyrazolone derivatives

Purpose: To synthesize new antimicrobial azo-pyrazolone derivatives III & IV and evaluate their antimicrobial activities using a combination of in vitro and molecular docking studies.Methods: Azopyrazolone compounds were prepared from the reaction of substituted aniline diazonium with ethyl acetoacetate to give azoxobutyric acid derivatives (II) which were then reacted with phenyl hydrazine or hydrazine hydrate. The pyrazolone derivatives (IV) were acetylated with glacial acetic acid to yield new acetylated pyrazolones (V). An agar dilution method was used to demonstrate the  antimicrobial activities of the pyrazolone derivatives and their minimum inhibitory concentration (MIC) values calculated. Molecular docking studies were employed to further evaluate the most active compounds (on the basis of the MICs obtained).Results: The new pyrazolone derivatives showed varying antimicrobial activities (from negligible to strong) against a number of microorganisms. Derivatives IIIb and Vb showed potent activities against Bacillus subtilis, Sarcina lutea, Staphylococcus aureus and Enterococcus faecalis. However, the new compounds did not show antifungal activity. Molecular docking results for compounds IIIb and Vb wereconsistent with their antimicrobial activities and proved that the compounds inhibited glucosamine-6-phosphate synthase.Conclusion: The new dichloropyrazolone compounds IIIa and Vb possess potent antimicrobial activities. These compounds have promising potential for use as new antibacterial agents or as templates for the design of new antimicrobial drugs.Keywords: Azo-pyrazolone, Dichloropyrazolone, Antimicrobial, Molecular dockin

Phytochemical Investigation of Egyptian Spinach Leaves, a Potential Source for Antileukemic Metabolites: In Vitro and In Silico Study

Spinacia oleracea L., Amaranthaceae, leaves cultivated in Egypt demonstrated a potential antileukemic activity against the chronic myeloid leukemia, K562 cell line. Thus, the aim of this study is to carry out a phytochemical investigation of S. oleracea leaves as well as the isolation of its antileukemic phytoconstituents. Phytochemical investigation of S. oleracea leaves resulted in the isolation of seventeen known compounds. The biological study revealed that compounds hexaprenol, phytol, and 18-[(1-oxohexadecyl) oxy]-9-octadecenoic acid exhibited a remarkable antiproliferative activity against K562 cells in vitro. A mechanistic in silico study showed that hexaprenol, phytol, and 18-[(1-oxohexadecyl) oxy]-9-octadecenoic acid exhibited a strong binding affinity towards topoisomerase (docking score −12.50, −9.19, and −13.29 kcal/mol, respectively), and showed as well a strong binding affinity towards Abl kinase (docking score −11.91, −9.35, and −12.59 kcal/mol, respectively). Molecular dynamics study revealed that 18-[(1-oxohexadecyl) oxy]-9-octadecenoic acid produced stable complexes with both topoisomerase and Abl kinase with RMSD values of 1.81 and 1.85 Å, respectively. As a result of our findings, we recommend more in vivo and preclinical studies to confirm the potential benefit of spinach leaves for chronic myeloid leukemia patients. Graphical Abstract: [Figure not available: see fulltext.

Synthesis, antimicrobial activities and GAPDH docking of novel 1, 2, 3-triazole derivatives

Purpose: To synthesize new triazole derivatives in order to overcome the problem of side effects of antimicrobial agents and microbial resistance, while broadening the spectrum of antimicrobial activity. Methods: The starting triazole, compound 1, was prepared through click chemistry and reacted with chloroacetyl chloride to yield compound II. Triazole 1 was reacted with acids and aldehydes to produce oxadiazole (III) and azomethine (IV) which cyclized in acetic anhydride to give a new acetylated oxadiazole (V). Minimum inhibitory concentration (MIC) and resorufin assays were used for antibacterial and anti-parasitic screening, respectively. Compounds II and IVb were subjected to molecular docking studies using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) Molecular Operating Environment (MOE) program. Results: Novel oxazole-triazole derivative (III) showed high activity against Pseudomonas aeruginosa and moderate activity against Staphylococcus epidermidis, whereas compound IVc showed moderate activity against Staphylococcus epidermidis. Chloro-acetyl-triazole II and 2-hydroxyphenyl-triazole Schiff base (Ivb) showed pronounced activity against the kinetoplastid parasites, Leishmania major, Leishmania mexicana and Trypanosoma brucei. Conclusion: The new synthesized triazoles represent a new antimicrobial scaffold and identifies potential new lead compounds for follow-up and for further mechanistic studies

Mitigation of acetaminophen-induced liver toxicity by the novel phosphatidylinositol 3-kinase inhibitor alpelisib

The sterile inflammatory response mediated by Toll-like receptors (TLRs) 4 and 9 is implicated in the massive hepatic damage caused by acetaminophen (APAP)-overdose. There is a crosstalk between TLR-dependent signaling with other intracellular kinases like phosphatidylinositol 3-kinases (PI3Ks). Nevertheless, the detailed role of PI3Kα is still unknown in hepatic sterile inflammation. Accordingly, the effect of the novel PI3Kα inhibitor alpelisib was investigated in the setting of APAP-driven sterile inflammation in the liver. This was examined by pretreating mice with alpelisib (5 and 10 mg/kg, oral) 2 h before APAP (500 mg/kg, i.p.)-intoxication. The results indicated that alpelisib dose-dependently lowered APAP-induced escalation in serum liver function biomarkers and hepatic necroinflammation score. Alpelisib also attenuated APAP-induced rise in cleaved caspase 3 and proliferating cell nuclear antigen (PCNA) in the liver hepatocytes, as indices for apoptosis and proliferation. Mechanistically, inhibition of PI3Kα by alpelisib limited APAP-induced overproduction of the pro-inflammatory tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in the blood circulation via switching off the activation of several signal transduction proteins, including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), signal transducer and activator of transcription-3 (Stat-3), glycogen Synthase Kinase (GSK)-3β and nuclear factor (NF)-κB. Alpelisib also impaired APAP-instigated immune cell infiltration in the liver via reducing systemic granulocyte/macrophage-colony stimulating factor (GM-CSF) release and reversed APAP-induced abnormalities in the systemic and hepatic levels of the anti-inflammatory IL-10 and IL-22. In conclusion, selective modulation of the PI3Kα activity by alpelisib can hinder the inflammatory response and infiltration of immune cells occurring by APAP-hepatotoxicity

Chitosan-Functionalized-Graphene Oxide (GO@CS) Beads as an Effective Adsorbent to Remove Cationic Dye from Wastewater

In this study, the preparation of graphene oxide@chitosan (GO@CS) composite beads was investigated via continuous dropping techniques to remove methylene blue (MB)-dye from an aqueous media. The prepared beads were characterized using various techniques before and after the adsorption of MB. The experimental results showed that the adsorption processes fit the kinetic pseudo-second-order and Langmuir isotherm models. Moreover, the GO@CS beads achieve maximum adsorption capacities of 23.26 mg g$^{−1}$, which was comparable with other adsorbents in the literature. An important advantage of our adsorbent is that the GO@CS can remove 82.1% of the real sample color within 135 min

Review of the Recent Advances in Electrospun Nanofibers Applications in Water Purification

Recently, nanofibers have come to be considered one of the sustainable routes with enormous applicability in different fields, such as wastewater treatment. Electrospun nanofibers can be fabricated from various materials, such as synthetic and natural polymers, and contribute to the synthesis of novel nanomaterials and nanocomposites. Therefore, they have promising properties, such as an interconnected porous structure, light weight, high porosity, and large surface area, and are easily modified with other polymeric materials or nanomaterials to enhance their suitability for specific applications. As such, this review surveys recent progress made in the use of electrospun nanofibers to purify polluted water, wherein the distinctive characteristics of this type of nanofiber are essential when using them to remove organic and inorganic pollutants from wastewater, as well as for oil/water (O/W) separation

Recent Progress and Potential Biomedical Applications of Electrospun Nanofibers in Regeneration of Tissues and Organs

Electrospun techniques are promising and flexible technologies to fabricate ultrafine fiber/nanofiber materials from diverse materials with unique characteristics under optimum conditions. These fabricated fibers/nanofibers via electrospinning can be easily assembled into several shapes of three-dimensional (3D) structures and can be combined with other nanomaterials. Therefore, electrospun nanofibers, with their structural and functional advantages, have gained considerable attention from scientific communities as suitable candidates in biomedical fields, such as the regeneration of tissues and organs, where they can mimic the network structure of collagen fiber in its natural extracellular matrix(es). Due to these special features, electrospinning has been revolutionized as a successful technique to fabricate such nanomaterials from polymer media. Therefore, this review reports on recent progress in electrospun nanofibers and their applications in various biomedical fields, such as bone cell proliferation, nerve regeneration, and vascular tissue, and skin tissue, engineering. The functionalization of the fabricated electrospun nanofibers with different materials furnishes them with promising properties to enhance their employment in various fields of biomedical applications. Finally, we highlight the challenges and outlooks to improve and enhance the application of electrospun nanofibers in these applications

High-Pressure Metal-Free Catalyzed One-Pot Two-Component Synthetic Approach for New 5-Arylazopyrazolo[3,4-b]Pyridine Derivatives

An appropriate and efficient Q-tube-assisted ammonium acetate-mediated protocol for the assembly of the hitherto unreported 5-arylazopyrazolo[3,4-b]pyridines was demonstrated. This methodology comprises the cyclocondensation reaction of 5-amino-2-phenyl-4H-pyrazol-3-one with an assortment of arylhydrazonals in an NH$_4$OAc/AcOH buffer solution operating a Q-tube reactor. This versatile protocol exhibited several outstanding merits: easy work-up, mild conditions, scalability, broad substrate scope, safety (the Q-tube kit is simply for pressing and sealing), and a high atom economy. Consequently, performing such reactions under elevated pressures and utilizing the Q-tube reactor seemed preferable for achieving the required products in comparison to the conventional conditions. Diverse spectroscopic methods and X-ray single-crystal techniques were applied to confirm the proposed structure of the targeted compounds