Introduction: COVID-19 is a new viral illness that can affect the lungs and airways with lethal consequences leading to the death of the patients. The ACE2 receptors were widely disturbed among body tissues such as lung, kidney, small intestine, heart, and others in different percent and considered a target for the nCOVID-19 virus. S-protein of the virus was binding to ACE2 receptors caused downregulation of endogenous anti-viral mediators, upregulation of NF-κB pathway, ROS and pro-apoptotic protein. Nrf2 was a transcription factor that's play a role in generation of anti-oxidant enzymes. Aim: To describe and establish role of Nrf2 activators for treatment COVID-19 positive patients. Methods: We used method of analysis of the published papers with described studies about COVID-19 connected with pharmacological issues and aspects which are included in global fighting against COVID-19 infection, and how using DMF (Nrf2 activator) in clinical trial for nCOVID-19 produce positive effects in patients for reduce lung alveolar cells damage. Results: we are found that Nrf2 activators an important medication that's have a role in reduce viral pathogenesis via inhibit virus entry through induce SPLI gene expression as well as inhibit TRMPSS2, upregulation of ACE2 that's make a competition with the virus on binding site, induce gene expression of anti-viral mediators such as RIG-1 and INFs, induce anti-oxidant enzymes, also they have a role in inhibit NF-κB pathway, inhibit both apoptosis proteins and gene expression of TLRs. Conclusion: We are concluded that use DMF (Nrf2 activator) in clinical trial for nCOVID-19 positive patients to reduce lung alveolar cells damage.
A variety of novel bicyclic and tricyclic pyrimidine derivatives was obtained via reaction of 6-amino-2-thioxo-1H-pyrimidine-4-one (1) with a different reagents. The antimicrobial and anti-inflammatory activities of some of the synthesized compounds were tested.
2-Thiouracil-5-sulphonic acid N-(4-acetylphenyl) Amide (1) was reacted with a series of aromatic aldehydes giving chalcones 2 (Claisen-Schemidt reaction), some of these chalcones were reacted with urea and thiourea giving pyrimidine-2-one and pyrimidine-2 thione derivatives respectively of the type 3a,b and 4a,b. In addition many chalcones were reacted with hydroxylamine hydrochloride giving isoxazoline derivatives 5a,b. They could also reacted with phenylhydrazine to give pyrazoline derivatives 6a,b, chalcones also were reacted withethylcyano acetate and/or malononitryl in pyridine giving pyran derivatives 7a,c and 8a,c. In another pathway chalcones were epoxidised by H2O2 giving epoxides 9a,c which in turn were reacted with phenylhydrazine giving 4-hydroxypyrazoline derivatives 10a,c. In another reaction chalcones were reacted with ethylcyanoacetate in presence of amm.acetate giving pyridone derivatives 11a,d which could be prepared also in exellent yield from compound 1 by its reaction with certain aromatic aldehydes and ethylcyanoacetate in presence of ammonium acetate. Finally, compound 1 was reacted with semicarbazide giving semicarbazone intermediate 12 which in turn was reacted with thionyl chloride giving thiadiazole derivative 13. The biological effects of some of the new synthesized compounds were also investigated.
Some new thiopyrimidine acyclic nucleosides and thioglycoside derivatives 3a-c, 4a-c, 6a,b, and 7a,b were synthesized. The cytotoxicity and antitumor evaluation of all prepared compounds have been tested in vitro against Ehrlich's ascites carcinoma cell line and their activity against glutathione peroxidase and catalase were reported. The role of the prepared compounds as free radical regulators and the therapeutic antitumor effect of a balanced generation of free radicals are discussed. Compounds 2, 3b, 3c, 4a, and 4c inhibited significantly in a dose dependent manner the growth of Ehrlich ascites carcinoma cells while the other compounds did not show any antitumor activity even at higher concentrations.
Oxidative stress is one of the main causes of significant severe diseases. The discovery of new potent antioxidants with high efficiency and low toxicity is a great demand in the field of medicinal chemistry. Herein, we report the design, synthesis molecular modelling and biological evaluation of novel hybrids containing pyrazole, naphthalene and pyrazoline/isoxazoline moiety. Chalcones 2a-e were synthesized efficiently and were used as starting materials for synthesis of a variety of heterocycles. A novel series of pyrazoline 3a-e, phenylpyrazoline 4a-e, isoxazoline 5a-e and pyrazoline carbothioamide derivatives 6a-e were synthesized and screened for in vitro antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO) and superoxide radical scavenging assay as well as 15-lipoxygenase (15-LOX) inhibition activity. Compounds 3a, 4e, 5b, 5c, 6a, 6c, and 6e showed excellent radical scavenging activity in all three methods in comparison with ascorbic acid and 15-LOX inhibition potency using quercetin as standard then were subjected to in vivo study. Catalase (CAT) activity, glutathione (GSH) and malondialdehyde (MDA) levels were assayed in liver of treated rats. Compounds 5b, 5c, and 6e showed significant in vivo antioxidant potentials compared to control group at dose of 100 mg/kg B.W. Molecular docking of compound 6a endorsed its proper binding at the active site pocket of the human 15-LOX which explains its potent antioxidant activity in comparison with standard ascorbic acid.
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