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In Vitro Antiamoebic Activity Evaluation and Docking Studies of Metronidazole–Triazole Hybrids
Author(s) -
Negi Beena,
Raj K. Kranthi,
Siddiqui Shadab Miyan,
Ramachandran Dittakavi,
Azam Amir,
Rawat Diwan S.
Publication year - 2014
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201402240
Subject(s) - docking (animal) , entamoeba histolytica , adme , metronidazole , triazole , active site , stereochemistry , chemistry , virtual screening , biochemistry , in vitro , combinatorial chemistry , biology , pharmacology , enzyme , drug discovery , microbiology and biotechnology , antibiotics , medicine , nursing , organic chemistry
Abstract An in‐house database of 520 compounds was docked against Entamoeba histolytica thioredoxin reductase ( Eh TrR), a promising target for the treatment of amoebiasis. Amongst these, some metronidazole (MTZ)–triazole hybrids were ranked high, with docking scores from −10.23 to −7.56. Studies of the binding orientations and conformations show that the head groups of MTZ–triazole hybrids interact with the arginine residues within the binding pocket of Eh TrR, making it clear that such is the optimal and most reliable orientation for this class of compounds. The top‐ten MTZ–triazole hybrids were then selected for evaluation of their activity against the HM1:IMSS strain of amoeba. The most active compound, 2‐pyridyl‐(1,2,3‐triazolyl)metronidazole 10 , with an IC 50 value of 8.4 n M , was significantly more active than the standard drug MTZ alone. Docking studies revealed that compound 10 may act as an Eh TrR inhibitor with activity in the nanomolar range and satisfactory ADME properties; it is a suitable candidate to be carried forward as a potential lead in the discovery of drugs to combat amoebiasis.