SYNTHESIS AND ANTIVIRAL ACTIVITY OF NOVEL ETHYL 2-(3-HETEROCYCLE-1H-INDOL-1-YL) ACETATE DERIVATIVES
Journal Title: International Journal of Pharmacy and Pharmaceutical Sciences - Year 2015, Vol 7, Issue 5
Abstract
ABSTRACTObjective: Marek's disease (MD) is a widespread, herpesvirus-induced neoplastic disease in the domestic chicken that is caused by Marek's disease virus (MDV). Marek’s disease virus (MDV) belongs to the alphaherpesvirus family such as Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2). Recently Bag and co-workers 2014 reported that, 7-methoxy-1-methyl-4, 9-dihydro-3H-pyrido [3, 4-b]indole (Harmaline) showed potent anti-HSV-1 activity against both wild type and clinical isolates of HSV-1. The present work aimed to synthesize some new heterocyclic systems incorporated to indole moiety starting from ethyl 2-(3-acetyl-1H-indol-1-yl)acetate (1) in order to evaluate their antiviral activity in a trail to explore potential antiviral agents against MDV to limit the disease course and losses.Methods: Reaction of ethyl 2-(3-acetyl-1H-indol-1-yl) acetate (1) with semicarbazide hydrochloride yielded semicarbazone derivative 2. The oxidative cyclization of 2 using thionyl chloride and selenium dioxide afforded 1, 2, 3-thia and 1, 2, 3-selenadiazole derivatives 3 and 4, respectively. On the other hand, reaction of 1 with 4-chloro and 4-nitrobenzaldehydes under Claisen-Schmidt conditions gave α, β-unsaturated keto derivatives 5a, b. Cyclization of 5a, b using hydrazine hydrate, phenyl hydrazine, urea, thiourea or guanidine led to the formation of pyrazoles 6a, b, 7a, b, and pyrimidines derivatives 8a, b-10a, b; respectively. Condensation of 1 with phenyl hydrazine followed by Vilsmeier Haack formylation gave pyrazole-4-carboxaldehyde derivative 12. Reaction of aldehydic function group of 12 with different reagents led to the formation of pyrazol-5-ones 14-16, thiazolidinone 18, aziditine 19, 1, 6-diaminopyridine 21, triazolo(1, 5-a)pyridine 22 and pyrano(2, 3-c) pyrazole derivatives 23. The in vitro antiviral activity of the selected compounds 6a, b 7a, b 8a, b 9a, b and 10a, b was studied against Marek's disease virus (MDV).Results: Chicken embryo experiment showed that compounds 7b, 8b, 9b and 10a possessed significant antiviral activity with IC50 ranged between 5 and 6 µg/ml and substantial therapeutic indices (TI) of 80 and 83 were recorded. Cytotoxicity assay indicated that CC50 of 7b, 8b, 9b and 10 were greater than 400 and 500 mg/ml.Conclusion: Compounds 7b, 8b, 9b and 10a showed promising effect as anti-MDV infectivity application.Â
Authors and Affiliations
Eslam R El-sawy, Heba M Abo-salem, Eman S Zarie, Howaida I Abd-alla, Mounir M El-safty, Adel H Mandour
Keywords
Related Articles
- EP ID EP578783
- DOI -
- Views 78
- Downloads 0
DEVELOPMENT AND VALIDATION OF RP-HPLC METHOD FOR THE DETERMINATION OF ALVIMOPAN IN RAT PLASMA
Objective: The present investigation demonstrates a simple, sensitive and accurate high pressure liquid chromatographic (HPLC) method for the determination of alvimopan (AMP) in rat plasma.Methods: The chromatographic se...
ASSESSMENT OF ANTIDIABETIC ACTIVITY OF THE TRADITIONAL INDIAN AYURVEDIC FORMULATION BRAHMI GRITHAM IN STREPTOZOTOCIN-INDUCED DIABETIC RATS
Objective: The aim of the present study was to determine the antidiabetic activity of Brahmi gritham a traditional Indian ayurvedic formulation in streptozotocin-induced diabetes in rats.Methods: Diabetes was induced by...
FORMULATION AND EVALUATION OF TOPICAL PENTOXIFYLLINE-HYDROXYPROPYL METHYLCELLULOSE GELS FOR WOUND HEALING APPLICATION
Objectives: Oral pentoxifylline shows modest, non-significant effect on the healing rates of chronic wounds. The present research aimed to formulate topical pentoxifylline-hydroxypropyl methylcellulose (HPMC) gels and ev...
EVIDENCES FOR THE PROMISING THERAPEUTIC POTENTIAL OF BOSWELLIA SERRATA AGAINST ALZHEIMER'S DISEASE: PRE-CLINICAL STUDY
Objective: The current study was planned to investigate the anti-inflammatory and antiapoptotic effects of Boswellia serrata methanolic extract against neurodegeneration characterizing Alzheimer’s disease (AD) in rat m...
BIOPROCESS MODELING FOR THE PREDICTION OF THERAPEUTIC ENZYME L-ASPARAGINASE ACTIVITY IN SOLID STATE FERMENTATION USING MULTIPLE LINEAR REGRESSION AND ANN
Objective: L-asparaginase is an enzyme of industrial as well as therapeutic importance. The capabilities of bioprocess modeling of L-Asparaginase activity produced from Aspergillus niger by solid state fermentation (SSF)...