Synthesis, Anti-Schistosomal Activity and Molecular Modeling of Two Novel 8-Hydroxyquinoline Derivatives
Ahmad F. Eweas,
Abdelaziz S.A. Abu-Elsaad,
Ibrahim A. Maghrabi,
Abdul Hamid ALGhamdi.
Schistosomiasis is one of the world’s greatly neglected tropical diseases, and its control is largely dependent on
a single drug, praziquantel (PZQ). Here, two novel 8-hydroxyqinoline-5-sulfonamido derivatives, compounds 3 and 4,
have been synthesized, characterized and tested as anti-schistosomal agents in vitro. Exposure of adult Schistosoma (S.)
mansoni adult worms to 200 µg/mL concentrations of either compound 3 or 4 reduced the motor activity and caused their
death within 24 hour (h). However, adult worms incubated in a medium containing 50 µg/mL of either compound 3 or 4
showed decrease motor activity and dead after 120 and 144 h of incubation, respectively. Different concentrations of both
compounds induced partial tegumental alterations in 40-50% of tested worms. Additionally, 50 µg/mL concentration of
compound 3 caused 58% and 75% reduction in egg production; however compound 4 caused 51% and 60% reduction in
oviposition after 48 and 72 h of incubation, respectively. Furthermore molecular docking of both 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 activity. The docking results revealed moderate to
high affinity of both compounds towards TGR. It is suggested that the in vitro schistosomicidal effects of our novel
8-hydroxyqinoline-5-sulfonamido derivatives may be related to the inhibition of TGR activity in S. mansoni. Our results
indicate the potential schistosomicidal effects of both 8-hydroxyqinoline derivatives.
Keywords: 8-hydroxyquinoline, Anti-schistosomal, Molecular docking, Thioredoxin-glutatione reductase (TGR).
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