Curcumin, a widely utilized flavor and coloring agent in food, has been shown to demonstrate powerful antioxidant, antitumor promoting and anti-inflammatory properties in vitro and in vivo. In the present work, synthesis of new heterocyclic derivatives based on Curcumin was studied. Compound 3 was synthesized via the reaction of furochromone carbaldehyde (1) with Curcumin (2) using pipredine as catalyst. Also, novel, 4,9-dimethoxy-5H-furo [3, 2-g] chromen-5-one derivatives 4a–d, 6a–d, 7, 8a–d, 9 and 10 were synthesized by the reactions of furochromone carbaldehyde (1) with different reagents (namely: appropriate amine 3a–d, appropriate hydrazine 5a–d, hydroxylamine hydrochloride, urea/thiourea, malononitrile, malononitrile with hydrazine hydrate). The structure of the synthesized products had been confirmed from their spectroscopic data (IR, 1H-NMR, 13C-NMR and mass spectra). In the present investigation, the newly synthesized products were screened using the MTT colorimetric assay for their in vitro inhibition capacity in two human cancer cell lines (hepatocellular carcinoma (HEPG2) and breast cancer (MCF-7) as well as the normal cell line (human normal melanocyte, HFB4) in comparison to the known anticancer drugs: 5-flurouracil and doxorubicin. The anticancer activity results indicated that the synthesized products 4c and 8b showed growth inhibition activity against HEPG2 cell line and synthesized products 4b and 8a showed growth inhibition activity against MCF-7, but with varying intensities in comparison to the known anticancer drugs, 5-flurouracil and doxorubicin. Cyclin dependent kinase 2 (CDK2), a major cell cycle protein, was identified as a potential molecular target of Curcumin. Furthermore, Curcumin induced G1 cell cycle arrest, which is regulated by CDK2 in cancer cells. Therefore, we used molecular modelling to study in silico the possible inhibitory effect of CDK2 by Curcumin derivatives as a possible mechanism of these compounds as anticancer agents. The molecular docking study revealed that compounds 4b, 8a and 8b were the most effective compounds in inhibiting CDk2, and, this result was in agreement with cytotoxicity assay.

Abstract:The reaction of methyl ketones 1a-g with dimethylformamide dimethylacetal (DMFDMA) afforded the enaminones 2a-g, which were coupled with diazotized aromatic amines 3a,b to give the corresponding aryl hydrazones 6a-h. Condensation of compounds 6a-h with some aromatic heterocyclic amines afforded iminoarylhydrazones 9a-m. Enaminoazo compounds 12a,b could be obtained from condensation of 6c with secondary amines. The reaction of 6e,h with benzotriazolylacetone yielded 14a,b. Also, the reaction of 6a,b,d-f,h with glycine and hippuric acid in acetic anhydride afforded pyridazinone derivatives 17a-f. Synthesis of pyridazine carboxylic acid derivatives 22a,b from the reaction of 6b,e with dimethyl acetylenedicarboxylate (DMAD) in the presence of triphenylphosphine at room temperature is also reported. Most of these reactions were conducted under irradiation in a microwave oven in the absence of solvent in an attempt to improve the product yields and to reduce the reaction times.

Utilization of 2-arylhydrazonopropanals for the synthesis of 2-arylhydrazonoimino propanones, 1,2,4-trizolo[4,3-a]pyrimidines, pyridopyridazine hydrazones, 3-oxaloalkanonitriles and 1,2,3-trizole derivatives by conventional heating and under microwave irradiation is described. Structural assignments are based on spectroscopic data and confirmed in some cases by X-ray crystallography.

Background: Coronavirus-19 (COVID-19) pandemic is a worldwide public health problem that has been known in China since December 25, 2019. Phospholipids are structural components of the mammalian cytoskeleton and cell membranes. They suppress viral attachment to the plasma membrane and subsequent replication in lung cells. In the virus-infected lung, phospholipids are highly prone to oxidation by reactive oxygen species, leading to the production of oxidized phospholipids (OxPLs). Objective: This study was carried out to explain the correlation between the level of plasma phospholipids in patients with COVID-19 infection and the levels of cytokine storms to assess the severity of the disease. Methods: Plasma samples from 34 enrolled patients with mild, moderate, and severe COVID-19 infection were collected. Complete blood count (CBC), plasma levels of D-dimer, ferritin, C-reactive protein (CRP), cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), phospholipids, secretory phospholipase A2 (sPLA2)α2, and cytokine storms were estimated, and lung computed tomography (CT) imaging was detected. Results: The CBC picture showed the presence of leukopenia, lymphopenia, and eosinopenia in patients with COVID-19 infection. Furthermore, a significant increase was found in plasma levels of D-dimer, CRP, ferritin, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-13 as well as sPLA2α2 activity compared to normal persons. However, plasma levels of phospholipids decreased in patients with moderate and severe COVID-19 infection, as well as significantly decreased in levels of triacylglycerols and HDL-C in plasma from patients with severe infection only, compared to normal persons. Furthermore, a lung CT scan showed the presence of inflammation in a patient with mild, moderate, and severe COVID-19 infection. Conclusions: This study shows that there is a correlation between plasma phospholipid depletion and elevated cytokine storm in patients with COVID-19 infection. Depletion of plasma phospholipid levels in patients with COVID-19 infection is due to oxidative stress, induction of cytokine storm, and systemic inflammatory response after endothelial cell damage promote coagulation. According to current knowledge, patients with COVID-19 infection may need to administer surfactant replacement therapy and sPLA2 inhibitors to treat respiratory distress syndrome, which helps them to maintain the interconnected surfactant structures.

Context: Quinazolines are a common class of nitrogen-containing heterocyclic scaffolds exhibiting a broad spectrum of pharmacological activities. Objective: In the present study, quinazoline and quinazolin-4-one derivatives were prepared, characterized to evaluate their biological which may pave the way for possible therapeutic applications. Materials amp; Methods: A new derivative of quinazoline and quinazolin-4-one derivatives was prepared and tested for antiulcerogenic, anti-inflammatory and hepatoprotective activity. Results: The synthesized compounds were characterized by elemental analysis and spectral data. Also, the median lethal doses (LD50s) of compounds 1-3 in rats were 1125, 835 and 1785 mg/kg b.w., respectively. IC50 values of compounds (1-3) as measured by ABTS+ radical method was 0.8, 0.92 and 0.08 mg/mL, respectively. Antiulcerogenic activities at dose 1/20 LD50 in albino rats were 47.94, 24.60 and 56.45%, respectively. Anti-inflammatory effect at dose 1/20 LD50 of compounds (1-3) induced edema model after 120 min. The prepared compounds possess hepato gastric mucosa protective activity against ibuprofen-induced ulceration and LPS-induced liver toxicity, respectively in rats via normalization of oxidative stress biomarkers and inflammatory mediators were inhibited in peritoneal macrophage cells at concentration of 100 µg/L. Molecular docking suggested that the most active compounds 1 and 2 can be positioned within the active sites of COX-2 at Arg121 & Tyr356 similar to ibuprofen (Arg-120, Glu-524, and Tyr-355). The compound 3–COX-2 complex generated by docking revealed intricate interactions with a COX-2 channel. Conclusion: These findings suggest that compounds 1-3 exhibited good antioxidant, antiulcer, anti-inflammatory activity and safe on liver enzymes in rats.

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A variety of arylhydrazonopyridinones were prepared via heating cyanoacetamides with ethyl acetoacetate in absence of solvent under reflux conventionally or ultrasound irradiation or in a microwave oven. The formed products 5 and 6 could be readily converted to thienopyridones. Attempted addition of the latter to electron poor olefins afforded only arylhydrazonopyridinones.

In this work, a new derivative of ethyl 5-chloro-2-(3-(4-hydroxyphenyl)propanamido)benzoate (1) was synthesized by reacting the amino group of 3-(4-hydroxyphenyl)propanoic acid (0.01 mol) and methyl 2-amino-5-chlorobenzoate in presence of PCl3. Cyclcondensation of 1 with hydrazine hydrate afforded the corresponding 2-(4-hydroxyphenethyl)-3-amino-6-chloroquinazolin-4(3H)-one (2). Also, new Schiff base 3 was prepared via reaction of 2-(4-hydroxyphenethyl)-3-amino-6-chloroquinazolin- 4(3H)-one (2) with 4-hydroxy-3-methoxybenzaldehyde. The synthesized compounds were characterized by elemental analysis, IR, 1H NMR and mass spectral data. Also, the median lethal doses (LD50s) of compounds 1-3 in rats were 1125, 835 and 1785 mg/kg b.w., respectively. IC50 values of compounds (1, 3) as measured by DPPH• method was 136.47 and 73.54 μg/mL, respectively. IC50 values of compounds (1-3) as measured by ABTS•+ radical method was 0.8, 0.92 and 0.08 mg/mL, respectively. Antiulcerogenic activity at dose 1/20 LD50 in albino rats was 47.94, 24.60 and 56.45%, respectively. However, the anti-inflammatory effect at dose 1/20 LD50 of compounds (1-3) induced edema model after 120 min were 74.19, 69.93 and 59.03%, respectively. The synthesized compounds also possess hepatocytes and gastric mucosa protective activity against ibuprofen induced ulceration and LPS-induced liver toxicity, respectively in rats via normalization of oxidative stress biomarkers and inflammatory mediators (Na+/K+-ATPase, ALT, AST, LDH, TNF-α, NO, TBARS, GPx, CAT and SOD). Also, TNF-α, NO, PGE2 and COX-2 were inhibited in peritoneal macrophage cells at a concentration of 100 μg/L. Molecular docking suggested that the most active compounds 1 and 2 can be positioned within the active sites of COX-2 at Arg121 & Tyr356 similarly to ibuprofen (Arg-120, Glu-524 and Tyr-355). The compound 3–COX-2 complex generated by docking, revealed intricate interactions with a COX-2 channel, including hydrogen bonds with key residues Arg121 and phe519. These findings suggest that compounds 1-3 exhibited good antioxidant, antiulcer, anti-inflammatory activity and safe on liver enzymes in rats.