Inhibitory effect of some new uracil and thiouracil derivatives on cercarial penetration enzymes

Inhibitory effect of some new uracil and thiouracil derivatives on cercarial penetration enzymes Some uracil- and thiouracil-5-sulfonohydrazide derivatives have been synthesized to be evaluated as antischistosomal agents. N-[2-(1,5-Dimethyl-3-oxo-2-phenylpyrazolin-4-yl)-4-oxo-1,3-thiazolidin-3-yl]-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonamide (3c) was formulated in jojoba oil and used to paint mice tails before infection with Schistosoma mansoni cercariae. Using Boc-Val-Leu-Gly-Arg-PNA, a specific substrate for trypsin-like serine proteinases, compound 3c inhibited cercarial serine protease activity with 50 % inhibition concentration (IC50) of 160 μg. Upon topical application on mice tails before infection with S. mansoni cercariae, it caused a 20 % reduction in worm burden compared with untreated infected mice. Using soluble crude cercarial antigen in enzyme-linked immunosorbent assay (ELISA), no significant changes were observed in the levels of immunoglobulin M (IgM) and IgG in sera from treated infected mice at 2, 4, and 6 weeks postinfection (WPI) compared with the level in sera from infected untreated mice. At 4 WPI, sera from treated infected mice showed significantly low (P < 0.05) IgM reactivity to crude soluble worm antigen compared with infected nontreated ones. IgG levels in sera from treated infected mice at 2 and 4 WPI were significantly lower (P < 0.05) than in sera from infected nontreated mice. At 6 WPI, the IgG response showed no significant differences in sera from both mice groups. Sera from treated infected mice at 2, 4, and 6 WPI had generally lower IgM reactivity to soluble egg antigen when compared with the level in sera from nontreated infected mice. At all time points postinfection, sera collected from treated infected mice showed significantly low IgG reactivity (P < 0.05) compared with infected nontreated mice. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Research on Chemical Intermediates Springer Journals

Inhibitory effect of some new uracil and thiouracil derivatives on cercarial penetration enzymes

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Publisher
Springer Journals
Copyright
Copyright © 2012 by Springer Science+Business Media B.V.
Subject
Chemistry; Catalysis; Physical Chemistry; Inorganic Chemistry
ISSN
0922-6168
eISSN
1568-5675
D.O.I.
10.1007/s11164-012-0748-x
Publisher site
See Article on Publisher Site

Abstract

Some uracil- and thiouracil-5-sulfonohydrazide derivatives have been synthesized to be evaluated as antischistosomal agents. N-[2-(1,5-Dimethyl-3-oxo-2-phenylpyrazolin-4-yl)-4-oxo-1,3-thiazolidin-3-yl]-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonamide (3c) was formulated in jojoba oil and used to paint mice tails before infection with Schistosoma mansoni cercariae. Using Boc-Val-Leu-Gly-Arg-PNA, a specific substrate for trypsin-like serine proteinases, compound 3c inhibited cercarial serine protease activity with 50 % inhibition concentration (IC50) of 160 μg. Upon topical application on mice tails before infection with S. mansoni cercariae, it caused a 20 % reduction in worm burden compared with untreated infected mice. Using soluble crude cercarial antigen in enzyme-linked immunosorbent assay (ELISA), no significant changes were observed in the levels of immunoglobulin M (IgM) and IgG in sera from treated infected mice at 2, 4, and 6 weeks postinfection (WPI) compared with the level in sera from infected untreated mice. At 4 WPI, sera from treated infected mice showed significantly low (P < 0.05) IgM reactivity to crude soluble worm antigen compared with infected nontreated ones. IgG levels in sera from treated infected mice at 2 and 4 WPI were significantly lower (P < 0.05) than in sera from infected nontreated mice. At 6 WPI, the IgG response showed no significant differences in sera from both mice groups. Sera from treated infected mice at 2, 4, and 6 WPI had generally lower IgM reactivity to soluble egg antigen when compared with the level in sera from nontreated infected mice. At all time points postinfection, sera collected from treated infected mice showed significantly low IgG reactivity (P < 0.05) compared with infected nontreated mice.

Journal

Research on Chemical IntermediatesSpringer Journals

Published: Aug 19, 2012

References

  • Infection induces antibodies against the cercarial secretions, but not against the cercarial elastases of Schistosoma mansoni, Schistosoma haematobium, Schistosoma japonicum, and Trichobilharzia ocellata
    Bahgat, M; Francklow, K; Doenhoff, MJ; Li, YL; Ramzy, RM; Kirsten, C; Ruppel, A

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