title: Metronidazole thiosalicylate conjugates: synthesis, crystal structure, docking studies and antiamoebic activity.
abstract: Metronidazole thiosalicylate conjugates were synthesized and crystallised in order to discover new molecules having better efficacy than therapeutically administered drug metronidazole, used against Entamoeba histolytica. The three compounds (4-6) showed lower IC(50) values than metronidazole on HM1:IMSS strain of E. histolytica and displayed low cytotoxicity on MCF-7 cell line. In order to get an insight into the mechanisms of action of these compounds, a homology model of E. histolytica thioredoxin reductase (EhTHRase) was constructed and molecular docking was performed into the binding pocket to identify the nature of interactions. The docking studies suggest that the improved inhibitory activity of the newly synthesised metronidazole analogues could be due to involvement of the additional hydrophobic interactions in the binding mode. The result of the present study indicates the molecular fragments that play an essential role in improving the antiamoebic activity.
authors: Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.
authors: Attar
authors: A
authors: Salahuddin
authors: Subhash M
authors: SM
authors: Agarwal
authors: Fernando
authors: F
authors: Avecilla
authors: Amir
authors: A
authors: Azam
mesh_terms: D000595:Amino Acid Sequence; D000977:Antiparasitic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001565:Benzoates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004748:Entamoeba histolytica / Q000187:drug effects* / Q000201:enzymology; D004749:Entamoebiasis / Q000188:drug therapy; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D008795:Metronidazole / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013849:Thimerosal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013880:Thioredoxin-Disulfide Reductase / Q000737:chemistry / Q000378:metabolism
chemical_list: D000977:Antiparasitic Agents; D001565:Benzoates; D013438:Sulfhydryl Compounds; D008795:Metronidazole; C026196:2-thiosalicylic acid; D013849:Thimerosal; D013880:Thioredoxin-Disulfide Reductase