Design and synthesis of new dihydropyrimidine/sulphonamide hybrids as promising anti-inflammatory agents via dual mPGES-1/5-LOX inhibition.

A novel series of dihydropyrimidine/sulphonamide hybrids 3a-j with anti-inflammatory properties have been developed and tested as dual mPGES-1/5-LOX inhibitors. In vitro assay, results showed that compounds 3c, 3e, 3h, and 3j were the most effective dual inhibitors of mPGES-1 and 5-LOX activities. Compound 3j was the most potent dual inhibitor with IC50 values of 0.92 µM and 1.98 µM, respectively. In vivo, anti-inflammatory studies demonstrated that compounds 3c, 3e, 3h, and 3e had considerable anti-inflammatory activity, with EI% ranging from 29% to 71%. Compounds 3e and 3j were equivalent to celecoxib after the first hour but exhibited stronger anti-inflammatory effects than celecoxib after the third and fifth hours. Moreover, compounds 3e and 3j significantly reduced the levels of pro-inflammatory cytokines (PGE2, TNF-α, and IL-6) with gastrointestinal safety profiles. Molecular docking simulations explored the most potent derivatives' binding affinities and interaction patterns within mPGES-1 and 5-LOX active sites. This study disclosed that compound 3j is a promising anti-inflammatory lead with dual mPGES-1/5-LOX inhibition that deserves further preclinical investigation.

Chitosan nanoparticles of new chromone-based sulfonamide derivatives as effective anti-microbial matrix for wound healing acceleration.

A new series of chromone and furochromone-based sulfonamide Schiff's base derivatives 3-12 were synthesized and evaluated for their antimicrobial activity against S. aureus, E. coli, C. albicans, and A. niger using agar diffusion method. Compound 3a demonstrated potent antimicrobial activities with MIC values of 9.76 and 19.53 µg/mL against S. aureus, E. coli and C. albicans, which is 2-fold and 4-fold more potent than neomycin (MIC = 19.53, 39.06 µg/mL respectively). To improve the effectiveness of 3a, it was encapsulated into chitosan nanoparticles (CS-3aNPs). The CS-3aNPs size was 32.01 nm, as observed by transmission electron microscope (TEM) images and the zeta potential value was 14.1 ± 3.07 mV. Encapsulation efficiency (EE) and loading capacity (LC) were 91.5 % and 1.6 %, respectively as indicated by spectral analysis. The CS-3aNPs extremely inhibited bacterial growth utilizing the colony-forming units (CFU). The ability of CS-3aNPs to protect skin wounds was evaluated in vivo. CS-3aNPs showed complete wound re-epithelialization, hyperplasia of the epidermis, well-organized granulation tissue formation, and reduced signs of wound infection, as seen through histological assessment which showed minimal inflammatory cells in comparison with untreated wound. Overall, these findings suggest that CS-3aNPs has a positive impact on protecting skin wounds from infection due to their antimicrobial activity.

Fifteen Years' Experience of Thoracoscopic Sympathetic Chain Interruption for Palmar Hyperhidrosis in Children and Adolescents: Evaluation of Different Techniques.

Background: Thoracoscopic sympathetic chain interruption is a definitive and effective therapy for severe primary palmar hyperhidrosis (PPH). Well-known methods include sympathectomy, sympathotomy, and clipping, but the occurrence of compensatory sweating offsets these methods. This study aims to report our experience with thoracoscopic sympathetic chain interruption in a large group of patients of age <18 years with PPH, focusing on surgical outcomes, complication rates, and patient satisfaction. Patients and Methods: This retrospective study included patients who underwent thoracoscopic sympathectomy, sympathotomy, or clipping for severe PPH between April 2008 and March 2023 at the Pediatric Surgery Department, Al-Azhar University Hospitals. Demographic and clinical data, operative steps, postoperative outcomes, complications, and patient satisfaction were reviewed from the patients' medical records. Results: During the 15-year study period, 420 children with PPH underwent bilateral thoracoscopic sympathetic chain interruption by either sympathectomy, sympathotomy, or clipping, with a sex ratio of 60% being females. The mean ages were 12 ± 3.48, 13 ± 2.45, and 13 ± 2.45 years, respectively. Sympathectomy was performed in 190 patients (45.2%), sympathotomy in 170 patients (40.5%), and clipping in 60 patients (14.3%). All patients had completed follow-up, with mean periods of ∼43 ± 5 months, 45 ± 3 months, and 42 ± 6 months, respectively. Complete palmar dryness was achieved in 405 patients (overall 96.4%) (97.8% after sympathectomy, 97.05% after sympathotomy, and 90% after clipping), whereas 2.1%, 2.9%, and 10% of patients experienced symptom recurrence, respectively, denoting significant statistical differences. Overall, 94 patients (22.4%) experienced compensatory sweating. Eventually, 409 patients (97.4%) were satisfied with the outcome, whereas 11 patients (2.6%) reported dissatisfaction, yet no significant differences found. Conclusion: The presented three modalities of thoracoscopic sympathetic chain interruption for PPH in children and adolescents are safe and effective, with overall very high postoperative satisfaction, despite a relatively high rate of compensatory sweating in sympathectomy group. Other major complications in this age population were scanty.

Synthesis of New D-π-A Phenothiazine-Based Fluorescent Dyes: Aggregation Induced Emission and Antibacterial Activity.

Highly solid-state fluorescent dyes based on phenothiazine bearing sulfa-drug derivatives were successfully prepared and fully characterized by NMR, mass spectra, and elemental analysis. The prepared phenothiazine dyes bearing sulfadiazine and sulfathiazole 4-(((10-hexyl-10 H-phenothiazin-3-yl)methylene)amino)-N-(pyrimidin-2yl) benzenesulfonamide (PTZ-1) and 4-(((10-hexyl-10 H-phenothiazin-3-yl) methylene) amino)-N-(thiazol-2-yl)benzenesulfonamide (PTZ-2), showed strong emission in polycrystalline form, and significant emission in solution was observed. The quantum yield of the prepared dyes varied and decreased by increasing the solvent polarity, with the maximum recorded value being 0.63 and 0.6 in dioxane. Aggregation-induced emission (AIE) and the effect of the solvent polarity on absorption and emission spectra were investigated. The dyeing application of polyester fabrics using the prepared phenothiazine-based dyes was studied, showing very good affinity to dyed fabrics. The antibacterial affinity against gram-positive and gram-negative bacteria for the dye powder as well as the dyed PET fabric was investigated, with PTZ-2 showing better affinity against bacteria compared to PTZ-1. This multifunctional property highlights the potential uses of PTZ-1 and PTZ-2 for advanced applications in biomedicine and optoelectronics.

Synthesis, biofilm formation inhibitory, and inflammation inhibitory activities of new coumarin derivatives.

Coumarins are heterocycles of great interest in the development of valuable active structures in chemistry and biological domains. The ability of coumarins to inhibit biofilm formation of Gram positive bacterium (Staphylococcus aureus), Gram negative bacterium (Escherichia coli) as well as the methicillin-resistant S. aureus (MRSA) has been previously described. In the present work, new hybrid coumarin-heterocycles have been synthesized via the reaction of coumarin-6-sulfonyl chloride and 6-aminocoumarin with different small heterocycle moieties. The biological efficacy of the new compounds was evaluated towards their ability to inhibit biofilm formation and their anti-inflammatory properties. The antimicrobial activities of the newly synthesized compounds were tested against Gram positive bacterium (S. aureus ATCC 6538), Gram negative bacterium (E. coli ATCC 25922), yeast (Candida albicans ATCC 10231) and the fungus (Aspergillus niger NRRL-A326). Compounds 4d, 4e, 4f, 6a and 9 showed significant MIC and MBC values against S. aureus, E. coli, C. albicans, and methicillin-resistant S. aureus (MRSA) with especial incidence on compound 9 which surpasses all the other compounds giving MIC and MBC values of (4.88 and 9.76 µg/mL for S. aureus), (78.13 and 312.5 µg/mL for E. coli), (9.77 and 78.13 µg/mL for C. albicans), and (39.06 and 76.7 µg/mL for MRSA), respectively. With reference to the antibiofilm activity, compound 9 exhibited potent antibiofilm activity with IC50 of 60, 133.32, and 19.67 µg/mL against S. aureus, E. coli, and MRSA, (respectively) considering the reference drug (neomycin). Out of all studied compounds, the anti-inflammatory results indicated that compound 4d effectively inhibited nitric oxide production in lipopolysaccharide-(LPS-) stimulated RAW264.7 macrophage cells, giving NO% inhibition of 70% compared to Sulindac (55.2%).

Ligand-based design and synthesis of new trityl histamine and trityl cysteamine derivatives as SIRT2 inhibitors for cancer therapy.

The relentless pursuit of novel therapeutic agents against cancer has led to the identification of multiple molecular targets, among which Sirtuin 2 (SIRT2) has garnered significant attention. This study presents an extensive SAR study of our reported trityl scaffold-based SIRT2 inhibitors. This study encompasses a range of different medicinal chemistry approaches to improve the activity of the lead compounds TH-3 and STCY1. The rationally designed and synthesized structures were confirmed using NMR and high-resolution mass spectroscopy before performing SIRT2 inhibition assay, NCI60 cytotoxicity test, and cell cycle analysis. Indeed, our strategies afforded hitherto unreported SIRT2 inhibitors with high activity, particularly 2a, 4a, 7c, and 7f. Remarkably, the presence of a lipophilic para substitution on the phenyl group of a freely rotating or a locked trityl moiety enhanced activity SIRT2 inhibition. Concomitantly, the synthesized compounds showed prominent activity against different cancer lines from the NCI60 assay. Of interest, compound 7c stands out as a potent and highly selective antiproliferative agent against leukemia and colon cancer panels. Furthermore, 7c treatment resulted in cell cycle arrest in MCF-7 cells at G2 phase and did not cause in vitro DNA cleavage.

Quinazoline-chalcone hybrids as HDAC/EGFR dual inhibitors: Design, synthesis, mechanistic, and in-silico studies of potential anticancer activity against multiple myeloma.

Two new series of quinazoline-chalcone hybrids were designed, synthesized as histone deacetylase (HDAC)/epidermal growth factor receptor (EGFR) dual inhibitors, and screened in vitro against the NCI 60 human cancer cell line panel. The most potent derivative, compound 5e bearing a 3,4,5-trimethoxyphenyl chalcone moiety, showed the most effective growth inhibition value against the panel of NCI 60 human cancer cell lines. Thus, it was selected for further investigation for NCI 5 log doses. Interestingly, this trimethoxy-substituted analog inhibited the proliferation of Roswell Park Memorial Institute (RPMI)-8226 cells by 96%, at 10 µM with IC50 = 9.09 ± 0.34 µM and selectivity index = 7.19 against normal blood cells. To confirm the selectivity of this compound, it was evaluated against a panel of tyrosine kinase enzymes. Mechanistically, it successfully and selectively inhibited HDAC6, HDAC8, and EGFR with IC50 = 0.41 ± 0.015, 0.61 ± 0.027, and 0.09 ± 0.004 µM, respectively. Furthermore, the selected derivative induced apoptosis via the mitochondrial apoptotic pathway by raising the Bax/Bcl-2 ratio and activating caspases 3, 7, and 9. Also, the flow cytometry analysis of RPMI-8226 cells showed that the trimethoxy-substituted analog produced cell cycle arrest in the G1 and S phases at 55.82%. Finally, an in silico study was performed to explore the binding interaction of the most active compound within the zinc-containing binding site of HDAC6 and HDAC8.

Antibacterial activity and dielectric properties of the PVA/cellulose nanocrystal composite using the synergistic effect of rGO@CuNPs.

This work aims to enhance the performance of the polyvinyl alcohol (PVA) composite by using cellulose nanocrystal (CNC) as reinforcement and copper nanoparticles (CuNPs)/reduced graphene oxide (rGO) as conducting and antimicrobial reagents. Firstly, rGO was loaded onto CuNPs using an eco-friendly microwave method. Different techniques characterized the components and prepared composites, which indicated the incorporation of cellulose nanocrystals and rGO@CuNPs within the polyvinyl alcohol matrix. Utilizing the clear zone of inhibition, the antibacterial test was quantified. Compared to the neat composite, the rGO@CuNPs loaded polyvinyl alcohol/ cellulose nanocrystal composites exhibited no bacterial growth against S. aureus, E. coli, and C. albicans. However, all composites did not have antifungal activity against A. niger. The combination of conductivity and interfacial polarization is the reason for the abrupt increase of permittivity with decreasing frequency. Besides, adding rGO@CuNPs improved the electrical conductivity. DC-Conductivity increased about a decade after adding cellulose nanocrystal to polyvinyl alcohol, then another decade after adding CuONPs. The electric loss modulus representation shows a systematic shift in the peak position towards higher frequencies, decreasing the so-called conductivity relaxation time. This is the main reason for the enhancement of conductivity. The systematic attenuation of peaks' height with increasing conductivity is still unclear.

Development of 1,5-diarylpyrazoles as EGFR/JNK-2 dual inhibitors: design, synthesis, moleecular docking, and bioactivity evaluation.

The eradication of multifactorial diseases, such as cancer, requires the design of drug candidates that attack multiple targets that contribute to the progression and proliferation of such diseases. Here, 1,5-diarylpyrazole derivatives bearing vanillin or sulfanilamide are developed as potential dual inhibitors of epidermal growth factor receptor (EGFR)/c-Jun N-terminal kinase 2 (JNK-2) for possible anticancer activity. These derivatives inhibited the growths of DLD-1, HeLa, K-562, SUIT-2 and HepG2 cancer cell lines, with minimum concentration required to inhibit half of the cellular growth (IC50) values of 2.7-63 µM. The tests confirmed that 5b and 5d were potent JNK-2 inhibitors, with IC50 of 2.0 and 0.9 µM, respectively, whereas 6 h selectively inhibited EGFR protein kinase (EGFR-PK) (IC50 = 1.7 µM). Notably, 6c inhibited both kinases, with IC50 values of 2.7 and 3.0 µM against EGFR-PK and JNK-2, respectively, offering a reference for designing mutual inhibitors of EGFR/JNK-2. The docking studies revealed the ability of the pyrazole ring to bind to the hinge region of the ATP binding site, thereby supporting the experimental inhibitory results. Furthermore, the developed compounds could induce apoptosis and induce cell cycle arrest at different cell phases.

Development of certain benzylidene coumarin derivatives as anti-prostate cancer agents targeting EGFR and PI3Kß kinases.

Novel coumarin derivatives were synthesised and tested for their cytotoxicity against human cancer cells (PC-3 and MDA-MB-231). Compounds 5, 4b, and 4a possessed potent cytotoxic activity against PC-3 cells with IC50 3.56, 8.99, and 10.22 µM, respectively. Compound 4c displayed cytotoxicity more than erlotinib in the MDA-MB-231 cells with IC50 8.5 µM. Moreover, compound 5 exhibited potent inhibitory activity on EFGR with IC50 0.1812 µM, as well as PI3Kß inhibitory activity that was twofold higher than LY294002, suggesting that this compound has a dual EGFR and PI3Kß inhibiting activity. Docking aligns with the in vitro results and sheds light on the molecular mechanisms underlying dual targeting. Furthermore, compound 5 decreased AKT and m-TOR expression in PC-3 cells, showing that it specifically targets these cells via the EGFR/PI3K/Akt/m-TOR signalling pathway. Simultaneously, compound 5 caused cell cycle arrest at S phase and induced activation of both intrinsic and extrinsic apoptotic pathways.

Short-term starvation at different feeding regimes on appetite responses, feeding utilization and physiological indices, of red hybrid tilapia (Oreochromis mossambicus × Oreochromis niloticus) fingerlings reared in brackish water.

A 42 day factorial trial (3x2) was designed to evaluate the effect of short-term starvation with different feeding frequencies on performance, feed utilization, physiological status and appetite responses of red hybrid tilapia fingerlings. Eighteen plastic tanks with a capacity of (55 L) were used to accomplish this work. Fingerlings with an average initial weight of 23 g ± 0.2 (SE) were randomly stocked at a rate of 8 fingerlings/aquarium. Six groups were designated as the following: II/ED: fish was fed twice every day; IV/ED: fish fed four times every day; II/EOD: fish fed twice every other day (alternate-day feeding or one day of feeding followed by another of fasting); IV/EOD: was fed four times every other day; II/EO3D: fish fed twice every other three days (three day of feeding followed by another of fasting) and IV/EO3D: fish fed four times every other three days. Fish were fed on commercial diets 30 % protein (4 % of biomass). Results showed insignificant differences between fish fed every other day and those fed every day in some growth indicators. In the same trend, the interaction between feed deprivation and feeding frequency cleared that fingerlings of IV/EOD did not significantly differ with those fed every day in growth indices. Moreover this treatment was the best in feed conversion efficiency and several physiological indicators.

Benzimidazole-Based Derivatives as Apoptotic Antiproliferative Agents: Design, Synthesis, Docking, and Mechanistic Studies.

A new class of benzimidazole-based derivatives (4a-j, 5, and 6) with potential dual inhibition of EGFR and BRAFV600E has been developed. The newly synthesized compounds were submitted for testing for antiproliferative activity against the NCI-60 cell line. All newly synthesized compounds 4a-j, 5, and 6 were selected for testing against a panel of sixty cancer cell lines at a single concentration of 10 µM. Some compounds tested demonstrated remarkable antiproliferative activity against the cell lines tested. Compounds 4c, 4e, and 4g were chosen for five-dose testing against 60 human tumor cell lines. Compound 4c demonstrated strong selectivity against the leukemia subpanel, with a selectivity ratio of 5.96 at the GI50 level. The most effective in vitro anti-cancer assay derivatives (4c, 4d, 4e, 4g, and 4h) were tested for EGFR and BRAFV600E inhibition as potential targets for antiproliferative action. The results revealed that compounds 4c and 4e have significant antiproliferative activity as dual EGFR/BRAFV600E inhibitors. Compounds 4c and 4e induced apoptosis by increasing caspase-3, caspase-8, and Bax levels while decreasing the anti-apoptotic Bcl2 protein. Moreover, molecular docking studies confirmed the potential of compounds 4c and 4e to act as dual EGFR/BRAFV600E inhibitors.

Production of laccase enzyme from Curvularia lunata MY3: purification and characterization.

Laccase-producing fungus (MY3) was successfully isolated from soil samples collected from Mansoura Governorate, Egypt. This fungal isolate has shown a high laccase production level over other isolated fungi. The identity of this isolate was determined by the molecular technique 18SrRNA as Curvularia lunata MY3. The enzyme purification was performed using ammonium sulfate precipitation followed by Sephacryl S-200 and DEAE-Sepharose column chromatography. The denatured enzyme using SDS-PAGE had a molar mass of 65 kDa. The purified laccase had an optimum temperature at 40 °C for enzyme activity with 57.3 kJ/mol activation energy for 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) oxidation. The enzyme had an optimum pH of 5.0, and it has shown a high stability at the acidic range (4.5 to 5.5). Mn2+ and Mg2+ ions enhanced the enzyme activity, while most of the enzyme activity was inhibited by Hg2+. Some compounds such as 2-mercaptoethanol, L-cysteine, and sodium azide at a concentration of 10 mmol/L had shown a high suppression effect on the enzyme activity. The enzyme strongly oxidized ABTS and syringaldazine and moderately oxidized DMP and guaiacol. The antimicrobial activity of the purified enzyme towards three pathogenic strains (Escherichia coli ATCC-25922, Staphylococcus aureus NRRLB-767, and Candida albicans ATCC-10231) was evaluated for the potential use as an antimicrobial therapeutic enzyme.

Quinazolin-4-one/3-cyanopyridin-2-one Hybrids as Dual Inhibitors of EGFR and BRAFV600E: Design, Synthesis, and Antiproliferative Activity.

A novel series of hybrid compounds comprising quinazolin-4-one and 3-cyanopyridin-2-one structures has been developed, with dual inhibitory actions on both EGFR and BRAFV600E. These hybrid compounds were tested in vitro against four different cancer cell lines. Compounds 8, 9, 18, and 19 inhibited cell proliferation significantly in the four cancer cells, with GI50 values ranging from 1.20 to 1.80 µM when compared to Doxorubicin (GI50 = 1.10 µM). Within this group of hybrids, compounds 18 and 19 exhibited substantial inhibition of EGFR and BRAFV600E. Molecular docking investigations provided confirmation that compounds 18 and 19 possess the capability to inhibit EGFR and BRAFV600E. Moreover, computational ADMET prediction indicated that most of the newly synthesized hybrids have low toxicity and minimal side effects.

Bioactive metabolites identified from Aspergillus terreus derived from soil.

Aspergillus terreus has been reported to produce many bioactive metabolites that possess potential activities including anti-inflammatory, cytotoxic, and antimicrobial activities. In the present study, we report the isolation and identification of A. terreus from a collected soil sample. The metabolites existing in the microbial ethyl acetate extract were tentatively identified by HPLC/MS and chemically categorized into alkaloids, terpenoids, polyketides, γ-butyrolactones, quinones, and peptides. In addition, a new triglyceride (1) and a diketopiperazine derivative namely asterrine (4), together with two known butyrolactone (2-3) were purified from the extract. The chemical skeleton of the purified compounds was established by comprehensive analysis of their ESI/MS, 1 and 2D-NMR data. The extract and compounds 3,4 exhibited a strong inhibitory activity for the binding of ACE2 to SARS-CoV-2 spike-protein receptor with IC50 7.4, 9.5, and 8.5 µg/mL, respectively. In addition, the extract, 1 and 2 displayed a potent anti-inflammatory effect with IC50 51.31 and 37.25 pg/mL (Il-6) and 87.97, 68.22 pg/mL (TNF-α), respectively, in comparison to LPS control. In addition, the extract and compound 4 displayed an antimicrobial effect towards S. aureus by MIC 62.5 and 125 µg/mL, while the extract exhibited a potent effect against C. albicans (MIC of 125 µg/mL). Collectively, our data introduce novel bioactivities for the secondary metabolites produced by the terrestrial fungus Aspergillus terreus.

Evaluation of fermented soybean meal by Bacillus subtilis as an alternative to fishmeal on the growth, and physiological status of Nile tilapia Oreochromis niloticus fingerlings.

A feeding trial was conducted to investigate the effect of fermented soybean meal with Bacillus subtilis bacteria on growth performance, feed utilization, carcass composition, and hematological, and histological section of the liver and intestine of Nile tilapia Oreochromis niloticus fingerlings. Commercial soybean meal (SBM) containing 44% Crude Protein (CP) was fermented using the solid-state fermentation method which depended on autoclaving of SBM, then bacterial treatment injection by Bacillus subtilis, and finally incubation at 40C for 72 h then autoclaved to stop the growth of bacteria. Five isonitrogenous (25% crude protein) and isocaloric (4.4 kcal\g gross energy) experimental fish meal-free diets were formulated to compare with a common control diet containing fishmeal and unfermented soybean meal. Diets without fish meal contain fermented soybean meal (FSM) as a sole protein, FSM with corn gluten (CG), FSM with free amino acid methionine (Meth), FSM with corn gluten and methionine, and unfermented soybean meal. Eighteen glass aquaria, 80-L net volume, were used to stock 10 fingerlings (10.0 ± 0.1 g/fish) in each aquarium in the replicates group. The feed amount was given three times daily, six days a week throughout the 98 days experimental period. Fish were weighed biweekly and feed amounts were adjusted based on the new fish weight. Bacterial fermentation enhanced the protein content of commercial soybean meals by 6%. The crude protein of fermented soybean meal increased from 43.44% to 50.67%. Used of FSM as a sole dietary protein source resulted in a decrease in growth rate and feed utilization. However, the incorporation of FSM with corn gluten, and/or methionine amino acid led to an improvement in the performance of fish. Finally, the best final body weight, weight gain, specific growth rate, protein efficiency ratio, and protein productive value were recorded by a fish-fed mixed plant protein diet (FSM + CG + Meth). Also, Hematocrit and red blood cells were not significantly affected including the FSM.

Chalcone/1,3,4-Oxadiazole/Benzimidazole hybrids as novel anti-proliferative agents inducing apoptosis and inhibiting EGFR & BRAFV600E.

INTRODUCTION: One of the most robust global challenges and difficulties in the 21st century is cancer. Treating cancer is a goal which continues to motivate researchers to innovate in design and development of new treatments to help battle the disease. OBJECTIVES: Our objective was developing new antiapoptotic hybrids based on biologically active heterocyclic motifs "benzimidazole?oxadiazole-chalcone hybrids'' that had shown promising ability to inhibit EGFR and induce apoptosis. We expected these scaffolds to display anticancer activity via inhibition of BRAF, EGFR, and Bcl-2 and induction of apoptosis through activation of caspases. METHODS: The new hybrids 7a-x were evaluated for their anti-proliferative, EGFR & BRAFV600E inhibitory, and apoptosis induction activities were detected. Docking study & dynamic stimulation into EGFR and BRAFV600E were studied. RESULTS: All hybrids exhibited remarkable cell growth inhibition on the four tested cell lines with IC50 ranging from 0.95 µM to 12.50 µM. which was comparable to Doxorubicin. Compounds 7k-m had the most potent EGFR inhibitory activity. While, compounds 7e, 7g, 7k and 7l showed good inhibitory activities against BRAFV600E. Furthermore, Compounds 7k, 7l, and 7m increased Caspases 3,8 & 9, Cytochrome C and Bax levels and decreased Bcl-2 protein levels. Compounds 7k-m received the best binding scores and showed binding modes that were almost identical to each other and comparable with that of the co-crystalized Erlotinib in EGFR and BRAF active sites. CONCLUSION: Compounds 7k-m could be used as potential apoptotic anti-proliferative agents upon further optimization.

A 47-Year-Old Woman with a Retained Central Venous Catheter Line Guidewire Presenting with a Right Atrial Thrombus Requiring Removal During Open Heart Surgery: A Case Report.

BACKGROUND A central venous catheter (CVC) is an indwelling catheter that is inserted into a large central vein for different purposes, including hemodynamic monitoring and administration of fluids and medications. This report is of a 47-year-old woman with a retained CVC line guidewire presenting with a large right atrial thrombus requiring removal during open heart surgery. CVC insertion is one of the most frequently attempted procedures in intensive care units, emergency departments, and operation rooms, especially for critically ill patients. Possible complications range from failure to place the catheter to cardiac arrest. One of the rarest complications is missing the guidewire after insertion, which is usually discovered early after inserting it. CASE REPORT We report the case of a 47-year-old woman who had a CVC line inserted following complicated open cholecystectomy. A few years later, she developed shortness of breath, with an incidental finding of a huge right atrial thrombus and a wire shown on transthoracic echocardiography. The right atrial thrombus required open heart surgery to excise the thrombus and the wire, which was done successfully. The thrombus was histopathologically and clinically proven to be an organized right atrial thrombus formed around the CVC guidewire. CONCLUSIONS This case report presents a rare complication of CVC insertion. Because this procedure is increasingly used, clinicians should be aware of the potential complications of retained CVC lines. Moreover, this report outlines different techniques to prevent such fatal complications and emphasizes the significance of radiography after insertion.

Development and Assessment of 1,5-Diarylpyrazole/Oxime Hybrids Targeting EGFR and JNK-2 as Antiproliferative Agents: A Comprehensive Study through Synthesis, Molecular Docking, and Evaluation.

New 1,5-diarylpyrazole oxime hybrid derivatives (scaffolds A and B) were designed, synthesized, and then their purity was verified using a variety of spectroscopic methods. A panel of five cancer cell lines known to express EGFR and JNK-2, including human colorectal adenocarcinoma cell line DLD-1, human cervical cancer cell line Hela, human leukemia cell line K562, human pancreatic cell line SUIT-2, and human hepatocellular carcinoma cell line HepG2, were used to biologically evaluate for their in vitro cytotoxicity for all the synthesized compounds 7a-j, 8a-j, 9a-c, and 10a-c. The oxime containing compounds 8a-j and 10a-c were more active as antiproliferative agents than their non-oxime congeners 7a-j and 9a-c. Compounds 8d, 8g, 8i, and 10c inhibited EGFR with IC50 values ranging from 8 to 21 µM when compared with sorafenib. Compound 8i inhibited JNK-2 as effectively as sorafenib, with an IC50 of 1.0 µM. Furthermore, compound 8g showed cell cycle arrest at the G2/M phase in the cell cycle analysis of the Hela cell line, whereas compound 8i showed combined S phase and G2 phase arrest. According to docking studies, oxime hybrid compounds 8d, 8g, 8i, and 10c exhibited binding free energies ranging from -12.98 to 32.30 kcal/mol at the EGFR binding site whereas compounds 8d and 8i had binding free energies ranging from -9.16 to -12.00 kcal/mol at the JNK-2 binding site.