Document Detail

Design, synthesis, anti-schistosomal activity and molecular docking of novel 8-hydroxyquinoline-5-sufonyl 1,4-diazepine derivatives.
MedLine Citation:
PMID:  23247256     Owner:  NLM     Status:  Publisher    
Schistosomiasis remains one of the most prevalent parasitic infections and has significant public health consequences. Praziquantel (PZQ) is the only drug currently administrated to treat this disease. However, praziquantel-resistant parasites have been identified in endemic areas and can be generated in the laboratory. Therefore, it is essential to find new therapeutics. Herein we report a series of novel 8-hydroxyquinoline-5-sufonyl 1,4-diazepine derivatives, which were synthesized, characterized and tested as anti-schistosomal agents in vitro. Among all tested compounds, compounds 4a, 5b, and 7b at different tested concentrations (50, 100, and 200μg/mL) showed the highest schistosomicidal activity. Among those 3 compounds, compound 7b was the most potent anti-schistosomal one. Moreover, all tested compound, at 50μg/mL concentration, significantly reduced oviposition of adult worms in vitro. Furthermore, both compound 4a and 7b, as well as compound 6a, completely diminished egg deposition. To clarify the possible mechanism by which novel 8-hydroxyquinoline-5-sufonyl 1,4-diazepine derivatives act as anti-schistosomal agents, molecular docking of all new compounds was carried out using Molsoft ICM pro 3.5-0a to investigate the binding affinity and binding mode to thioredoxin glutathione reductase enzyme (TGR), a potential drug target for anti-schistosomal agents. The docking results revealed moderate to high affinity of the new compounds towards TGR. Compound 7b scored the highest binding energy (-101.13kcal/mol) against TGR crystal structure forming eight hydrogen bonds with the amino acid residues at the binding site of the receptor. This result indicates that compound 7b could exert its effect through inhibition of TGR, which is a vital enzyme for schistosome survival.
Ahmad F Eweas; Gamal Allam; Abdelaziz S A Abuelsaad; Abdul Hamid Alghamdi; Ibrahim A Maghrabi
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-8
Journal Detail:
Title:  Bioorganic chemistry     Volume:  46C     ISSN:  1090-2120     ISO Abbreviation:  Bioorg. Chem.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-12-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1303703     Medline TA:  Bioorg Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  17-25     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Department of Medicinal Chemistry, National Research Center, Dokki, Cairo, Egypt; College of Pharmacy, Taif University, Taif, Saudi Arabia. Electronic address:
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