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Inhibitory Effects of Substituted Pyrazoline Derivatives on Entamoeba histolytica
Author(s) -
Tight Alexander,
Rossi Lauren,
Espinosa Avelina
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.607.4
Subject(s) - entamoeba histolytica , metronidazole , enzyme , amoebiasis , entamoeba , pharmacology , chemistry , medicine , biology , microbiology and biotechnology , biochemistry , antibiotics
Entamoeba histolytica is an intestinal parasite that causes disease in humans. Amoebiasis is a major public health risk, with about 50 million cases, and 100,000 deaths per year worldwide. The disease is primarily treated with metronidazole, which is effective but has adverse side effects such as neurological complications. Previous work in our laboratory generated 25 compounds within three series of pyrazoline derivatives that block the bifunctional enzyme alcohol dehydrogenase 2 (EhADH2). We tested these compounds in their ability to inhibit growth and survival of Entamoeba histolytica trophozoites. The inhibitors were tested at 60 and 120 μM concentrations and compared to the drug of choice metronidazole. Our results demonstrate that series 1a and 1b are the most effective. Compared to series 2, these series are significantly less bulky which could give the compound a greater affinity to bind to the enzyme. Although compounds from series 1b show greater growth inhibition, more data is needed to establish the relevance of each structural moiety. Future studies will test the efficiency in blocking the essential ADHE metabolic enzyme in Entamoeba and toxicity in human cells in comparison to metronidazole. Support or Funding Information Supported by Rhode Island National Institutes of Health INBRE Grant