Synthesis and antiviral activity of novel ethyl 2-(3-heterocycle-1H-indol-1-YL) acetate derivatives

Eslam R. El-Sawy, Heba M. Abo-Salem*, Eman S. Zarie, Howaida I. Abd-Alla, Mounir M. El-Safty, Del H. Mandour

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

3 Citations (Scopus)

Abstract

Objective: 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.

Original languageEnglish
Pages (from-to)76-83
Number of pages8
JournalInternational Journal of Pharmacy and Pharmaceutical Sciences
Volume7
Issue number5
Publication statusPublished - 2015
MoE publication typeA1 Journal article-refereed

Keywords

  • Ethyl 2-(3-acetyl-1H-indol-1-yl) acetate
  • Pyrazole
  • Pyridine
  • Pyrimidine Marek's disease virus (MDV)

Fingerprint

Dive into the research topics of 'Synthesis and antiviral activity of novel ethyl 2-(3-heterocycle-1H-indol-1-YL) acetate derivatives'. Together they form a unique fingerprint.

Cite this