Role of BAL cellularity in assessment of severity of idiopathic pulmonary fibrosis

Background/aim: Study the role of BAL cellularity in assessment of the degree of severity of IPF. Methods: Forty IPF patients underwent, history taking, clinical examination, HRCT chest, ABGs, 6MWT, spirometry, echocardiography, FOB and BAL. Results: Neutrophils were present in 28 patients, mean value 57.25 and SD ± 31.27. The second predominant cell was Alveolar Macrophages with mean value 24.25 and SD ± 27.828.HRCT pattern and BAL cellularity, showed the most predominant cell neutrophils in the ground glass and Honey combing on HRCT. There was no statistical significance between the sex and the BAL cellularity, the most predominant cell was neutrophils in both sexes. Corticosteroids did not have an effect on BAL cellularity and the predominant cell was neutrophils in IPF patients using steroids and those not. BAL cellularity in relation to treatment by azathioprine and/or acetlycysteine showed no statistical significance between patients using those drugs and those not, the most predominant cell was neutrophils in both groups.Correlation between BAL cellularity and age, showed no statistical significance but there was a negative correlation between age to neutrophils and lymphocytes. There was a negative correlation between neutrophils and PaCO2, PaO2, SO2, FVC%, FEV1 and 6MWT with no statistical significance but with significance to FEF25–75%.Macrophages showed a positive correlation with age, PaO2, 6MWT, FVC%, FEV1% with no statistical significance but with significance to SO2 and FEF25–75% and a negative correlation with PaCO2 and PASP. Conclusion: There was a positive correlation between neutrophils and severity of the disease and a negative correlation between Macrophages and severity of the disease. Most commonly used drugs did not show any effect on BAL cellularity

Structural and Spectroscopic Characteristics of NiII and CuII Complexes with Poly (Vinyl Alcohol-Nicotinic Acid) Copolymers for Photocatalytic Degradation of Indigo Carmine Dye

Poly-vinyl-alcohol (PVA) has been cross-linked chemically with nicotinic-acid (NA) in an aqueous medium. The copolymers were complexed with NiII and CuII ions. The complexes and copolymers were analyzed using FT-IR and UV–Visible spectroscopy, XRD and TGA, but copolymers were extra analyzed with nuclear magnetic resonance (1H NMR). FT-IR spectra of copolymer revealed the presence of C=O & C–N groups due to the esterification of PVA-NA. The Cu/NA-PVA formed via bidentate interaction of the pyridinyl and carboxyl of NA. EPR/UV-vis data shows the square-planar geometry for NiII and CuII complexes. The adsorption of IC dye onto CuII/NA-PVA complex was noticeably greater (90%) in 35 min than NiII/NA-PVA. The DFTB3LYP with 6- 311G* quantum chemical calculations were carried out for tested compounds. The DFT was conducted to examine an interaction mode of the target compounds with the reaction system. The QSPR was calculated as: optimization geometries, (FMOs), chemical-reactivities and NLO for the copolymers. The (MEPs) were figured to predict the interaction behavior of the ligand and its complexes

Discovery Potent of Thiazolidinedione Derivatives as Antioxidant, α-Amylase Inhibitor, and Antidiabetic Agent

This work aimed to synthesize safe antihyperglycemic derivatives bearing thiazolidinedione fragment based on spectral data. The DFT theory discussed the frontier molecular orbitals (FMOs), chemical reactivity of compounds, and molecular electrostatic potential (MEP) to explain interaction between thiazolidinediones and the biological receptor. α-amylase is known as the initiator-hydrolysis of the of polysaccharides; therefore, developing α-amylase inhibitors can open the way for a potential diabetes mellitus drug. The molecular docking simulation was performed into the active site of PPAR-γ and α-amylase. We evaluated in vitro α-amylase’s potency and radical scavenging ability. The compound 6 has the highest potency against α-amylase and radical scavenging compared to the reference drug and other members. They have been applied against anti-diabetic and anti-hyperlipidemic activity (in vivo) based on an alloxan-induced diabetic rat model during a 30-day treatment protocol. The most potent anti hyperglycemic members are 6 and 11 with reduction percentage of blood glucose level by 69.55% and 66.95%, respectively; compared with the normal control. Other members exhibited moderate to low anti-diabetic potency. All compounds showed a normal value against the tested biochemical parameters (CH, LDL, and HDL). The ADMET profile showed good oral bioavailability without any observed carcinogenesis effect

Thiazolidinedione Derivatives: In Silico, In Vitro, In Vivo, Antioxidant and Anti-Diabetic Evaluation

This work aimed to synthesize a new antihyperglycemic thiazolidinedione based on the spectral data. The DFTB3LYP6-311G** level of theory was used to investigate the frontier molecular orbitals (FMOs), chemical reactivity and map the molecular electrostatic potentials (MEPs) to explain how the synthesized compounds interacted with the receptor. The molecular docking simulations into the active sites of PPAR-γ and α-amylase were performed. The in vitro potency of these compounds via α-amylase and radical scavenging were evaluated. The data revealed that compounds (4–6) have higher potency than the reference drugs. The anti-diabetic and anti-hyperlipidemic activities for thiazolidine-2,4-dione have been investigated in vivo using the alloxan-induced diabetic rat model along with the 30 days of treatment protocol. The investigated compounds didn’t show obvious reduction of blood glucose during pre-treatments compared to diabetic control, while after 30 days of treatments, the blood glucose level was lower than that of the diabetic control. Compounds (4–7) were able to regulate hyperlipidemia levels (cholesterol, triglyceride, high-density lipoproteins and low- and very-low-density lipoproteins) to nearly normal value at the 30th day

Mosquitocidal Activity of the Methanolic Extract of <em>Annickia</em><em> chlorantha</em> and Its Isolated Compounds against <em>Culex pipiens</em>, and Their Impact on the Non-Target Organism Zebrafish, <em>Danio rerio</em>

In this study, the crude extract and its isolated compounds from the stem bark of Annickia chlorantha were tested for their larvicidal, developmental, and repellent activity against the mosquito vector, Culex pipiens, besides their toxicity to the non-target aquatic organism, the zebrafish (Danio rerio). The acute larvicidal activity of isolated compounds; namely, palmatine, jatrorrhizine, columbamine, β-sitosterol, and Annickia chlorantha methanolic extract (AC), was observed. Developmentally, the larval duration was significantly prolonged when palmatine and β-sitosterol were applied, whereas the pupal duration was significantly prolonged for almost all treatments except palmatine and jatrorrhizine, where it shortened from those in the control. Acetylcholinesterase (AChE) enzyme showed different activity patterns, where it significantly increased in columbamine and β-sitosterol, and decreased in (AC), palmatine, and jatrorrhizine treatments, whereas glutathione S-transferase (GST) enzyme was significantly increased when AC methanolic extract/isolated compounds were applied, compared to the control. The adult emergence percentages were significantly decreased in all treatments, whereas tested compounds revealed non-significant (p > 0.05) changes in the sex ratio percentages, with a slight female-to-male preference presented in the AC-treated group. Additionally, the tested materials revealed repellence action; interestingly, palmatine and jatrorrhizine recorded higher levels of protection, followed by AC, columbamine, and β-sitosterol for 7 consecutive hours compared to the negative and positive control groups. The non-target assay confirms that the tested materials have very low toxic activity compared to the reported toxicity against mosquito larvae. A docking simulation was employed to better understand the interaction of the isolated compounds with the enzymes, AChE and GST. Additionally, DFT calculations revealed that the reported larvicidal activity may be due to the differing electron distributions among tested compounds. Overall, this study highlights the potential of A. chlorantha extract and its isolated compounds as effective mosquitocidal agents with a very low toxic effect on non-target organisms

Synthesis and Biological Evaluation of 1,2,3-Triazole Tethered Thymol-1,3,4-Oxadiazole Derivatives as Anticancer and Antimicrobial Agents

A library of 1,2,3-triazole-incorporated thymol-1,3,4-oxadiazole derivatives (6–18) hasbeen synthesized and tested for anticancer and antimicrobial activities. Compounds 7, 8, 9, 10, and 11 exhibited significant antiproliferative activity. Among these active derivatives, compound 2-(4-((5-((2-isopropyl-5-methylphenoxy)methyl)-1,3,4-oxadiazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)phenol (9) was the best compound against all three tested cell lines, MCF-7 (IC50 1.1 μM), HCT-116 (IC50 2.6 μM), and HepG2 (IC50 1.4 μM). Compound 9 was found to be better than the standard drugs, doxorubicin and 5-fluorouracil. These compounds showed anticancer activity through thymidylate synthase inhibition as they displayed significant TS inhibitory activity with IC50 in the range 1.95–4.24 μM, whereas the standard drug, Pemetrexed, showed IC50 7.26 μM. The antimicrobial results showed that some of the compounds (6, 7, 9, 16, and 17) exhibited good inhibition on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The molecular docking and simulation studies supported the anticancer and antimicrobial data. It can be concluded that the synthesized 1,2,3-triazole tethered thymol-1,3,4-oxadiazole conjugates have both antiproliferative and antimicrobial potential

Cell Cycle Arrest and Apoptosis-Inducing Ability of Benzimidazole Derivatives: Design, Synthesis, Docking, and Biological Evaluation

In the current study, new benzimidazole-based 1,3,4-oxadiazole derivatives have been synthesized and characterized by NMR, IR, MS, and elemental analysis. The final compounds were screened for cytotoxicity against MDA-MB-231, SKOV3, and A549 cell lines and EGFR for inhibitory activities. Compounds 10 and 13 were found to be the most active against all the tested cell lines, comparable to doxorubicin, and exhibited significant inhibition on EGFR kinase, with IC50 0.33 and 0.38 μM, respectively, comparable to erlotinib (IC50 0.39 μM). Furthermore, these two compounds effectively suppressed cell cycle progression and induced cell apoptosis in MDA-MB-231, SKOV3, and A549 cell lines. The docking studies revealed that these compounds showed interactions similar to erlotinib at the EGFR site. It can be concluded that the synthesized molecules effectively inhibit EGFR, can arrest the cell cycle, and may trigger apoptosis and therefore, could be used as lead molecules in the development of new anticancer agents targeting EGFR kinase

Naproxen Based 1,3,4-Oxadiazole Derivatives as EGFR Inhibitors: Design, Synthesis, Anticancer, and Computational Studies

A library of novel naproxen based 1,3,4-oxadiazole derivatives (8–16 and 19–26) has been synthesized and screened for cytotoxicity as EGFR inhibitors. Among the synthesized hybrids, compound2-(4-((5-((S)-1-(2-methoxynaphthalen-6-yl)ethyl)-1,3,4-oxadiazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)phenol(15) was the most potent compound against MCF-7 and HepG2cancer cells with IC50 of 2.13 and 1.63 µg/mL, respectively, and was equipotent to doxorubicin (IC50 1.62 µg/mL) towards HepG2. Furthermore, compound 15 inhibited EGFR kinase with IC50 0.41 μM compared to standard drug Erlotinib (IC50 0.30 μM). The active compound induces a high percentage of necrosis towards MCF-7, HePG2 and HCT 116 cells. The docking studies, DFT and MEP also supported the biological data. These results demonstrated that these synthesized naproxen hybrids have EGFR inhibition effects and can be used as leads for cancer therapy