Inhibitors of Escherichia coli serine acetyltransferase block proliferation of Entamoeba histolytica trophozoites.
The protozoan parasite Entamoeba histolytica is the etiologic agent of amebiasis, a major global public health problem, particularly in developing countries. There is an effective anti-amoebic drug available, however its long term use produces undesirable side effects. As E. histolytica is a micro-aerophilic organism, it is sensitive to high levels of oxygen and the enzymes that are involved in protecting against oxygen-stress are crucial for its survival. Therefore serine acetyltransferase, an enzyme involved in cysteine biosynthesis, was used as a target for identifying potential inhibitors. Virtual screening with Escherichia coli serine acetyltransferase was carried out against the National Cancer Institute chemical database utilizing molecular docking tools such as GOLD and FlexX. The initial analysis yielded 11 molecules of which three compounds were procured and tested for biological activity. The results showed that these compounds partially block activity of the E. coli enzyme and the growth of E. histolytica trophozoites but not mammalian cells.
Agarwal
Subhash M
SM
Centre for Computational Biology and Bioinformatics, School of Information Technology, Jawaharlal Nehru University, New Mehrauli Road, New Delhi 110067, India. smagarwal@yahoo.com
Jain
Ruchi
R
Bhattacharya
Alok
A
Azam
Amir
A
D000818:Animals; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D030562:Databases, Protein; D004748:Entamoeba histolytica / Q000502:physiology*; D004749:Entamoebiasis / Q000517:prevention & control; D004926:Escherichia coli / Q000201:enzymology*; D005818:Genetic Engineering; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D051050:Serine O-Acetyltransferase / Q000037:antagonists & inhibitors* / Q000235:genetics; D053058:Trophozoites / Q000187:drug effects
D000981:Antiprotozoal Agents; D051050:Serine O-Acetyltransferase