Design, synthesis, ADME, biological evaluation and molecular dynamic studies of natural and synthetic remedy of Herpes simplex virus type-1.

Garlic (known as; Allium sativum) is one of the most widely used medicinal plants in the world. Allicin is the major agent of garlic that gives its known pharmacological activities as anti-inflammatory, antibacterial, antifungal, antiviral and antioxidant agent. It could be extracted from bulbs of Allium sativum by water extraction to give allicin in low yield therefore other better methods were followed for extraction such as ultrasonic-assisted method that gives good yield. Attempts to optimize allicin extraction were found with sliced garlic at 25 °C for 90 minute of extraction for maximum yield (112µg/mL). Allicin was subjected to its evaluation as anti-herpetic against herpes simplex virus 1 (HSV-1) and exhibited a promising activity compared to acyclovir which was used as a reference standard. On the other hand, a novel synthetic amantadine derivative was evaluated as antiherpetic agent and prepared from the reaction of 2-thiouracil-5-sulphonyl chloride with amantadine hydrochloride in pyridine. The synergestic effect of allicin and the amantadine derivative was evaluated against HSV-1, using both in silico molecular docking as for dynamics simulations. Thymidine kinase target enzyme was chosen to analyze any possible interactions, as well as any protein-ligand stability. Furthermore, some of properties of the potential HSV-1 thymidine kinase target inhibitor of the amantadine derivative were analyzed.

Synthesis and Evaluation of Some Uracil Nucleosides as Promising Anti-Herpes Simplex Virus 1 Agents.

Since herpes simplex virus type 1 (HSV-1) infection is so widespread, several antiviral drugs have been developed to treat it, among which are uracil nucleosides. However, there are major problems with the current medications such as severe side-effects and drug resistance. Here we present some newly synthesized cyclic and acyclic uracil nucleosides that showed very promising activity against HSV-1 compared to acyclovir.

The Nrf2 Activator (DMF) and Covid-19: Is there a Possible Role?

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.

Design, synthesis, molecular modelling and biological evaluation of novel 3-(2-naphthyl)-1-phenyl-1H-pyrazole derivatives as potent antioxidants and 15-Lipoxygenase inhibitors.

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.

Synthesis and antimicrobial evaluation of some 6-aryl-5-cyano-2-thiouracil derivatives.

A series of 6-aryl-5-cyano-2-thiouracil derivatives (1a-d) was synthesized by the reaction of ethyl cyanoacetate with thiourea and aldehydes. These products were used as intermediate compounds for the synthesis of a number of thiouracil derivatives (2a-d to 10a-d). All compounds were screened for antibacterial and antifungal activities. Some of the prepared compounds, 6-(4-fluorophenyl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide (2a), 4-oxo-2-thioxo-6-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydropyrimidine-5-carboxamide (2d), 6-(4-fluorophenyl)-4-hydrazino-2-thioxo-1,2-dihydropyrimidine-5-cabonitrile (7a) and 4-hydrazino-2-thioxo-6-(3,4,5-trimethoxyphenyl)-1,2-dihydropyrimidine-5-carbonitrile (7d) revealed promising antimicrobial activity.