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Inhibitory Effects of Substituted Pyrazoline Derivatives on Entamoeba histolytica Alcohol and Acetaldehyde Dehydrogenase ( Eh ADH2) Activities
Author(s) -
Hackey Meagan,
Rossi Lauren,
Espinosa Avelina
Publication year - 2017
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.31.1_supplement.921.4
Subject(s) - acetaldehyde , alcohol dehydrogenase , entamoeba histolytica , enzyme , biochemistry , phosphofructokinase 2 , glycolysis , aldehyde dehydrogenase , chemistry , biology , ethanol , microbiology and biotechnology
E. histolytica is a parasitic protist causing amebiasis in approximately fifty million people and 100,000 deaths worldwide annually. The bifunctional alcohol and acetaldehyde dehydrogenase Eh ADH2 enzyme is essential for E. histolytica trophozoite growth and survival as it is paramount in the glycolytic metabolic pathway. This enzyme is responsible for the conversion of acetyl co‐enzyme‐A to acetaldehyde and for the conversion of acetaldehyde to the final end product ethanol in the anaerobic pathogen. A thorough understanding of the role of this enzyme and its function will aid in the development of more effective chemical inhibitors for a better management of this deadly disease. We have generated three sets of first generation synthetic pyrazolines. Preliminary results show that three of the four series of compounds have inhibitory properties. Given the very high in vitro growth inhibition rates of these compounds and their mechanism of action, the target for these compounds seems to be Eh ADH2. Efficient pyrazolines will be tested for efficiency and specificity against purified Eh ADH2 and optimal inhibitory concentrations will be determined. This study will provide crucial and unique knowledge for more efficient chemotherapeutic targeting of ADHE enzymes. ADHE‐targeting agents could effectively treat a broad range of human diseases.