title: Novel diphenyl ethers: design, docking studies, synthesis and inhibition of enoyl ACP reductase of Plasmodium falciparum and Escherichia coli.
abstract: We designed some novel diphenyl ethers and determined their binding energies for Enoyl-Acyl Carrier Protein Reductase (ENR) of Plasmodium falciparum using Autodock. Out of these, we synthesized the promising compounds and tested them for their inhibitory activity against ENRs of P. falciparum as well as Escherichia coli. Some of these compounds show nanomolar inhibition of PfENR and low micromolar inhibition of EcENR. They also exhibit low micromolar potency against in vitro cultures of P. falciparum and E. coli. The study of structure-activity relationship of these compounds paves the way for further improvements in the design of novel diphenyl ethers with improved activity against purified enzyme and the pathogens.
authors.affiliation: Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India.
authors.forename: Manmohan
authors.initials: M
authors.lastname: Chhibber
authors.forename: Gyanendra
authors.initials: G
authors.lastname: Kumar
authors.forename: Prasanna
authors.initials: P
authors.lastname: Parasuraman
authors.forename: T N C
authors.initials: TN
authors.lastname: Ramya
authors.forename: Namita
authors.initials: N
authors.lastname: Surolia
authors.forename: Avadhesha
authors.initials: A
authors.lastname: Surolia
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D003198:Computer Simulation; D015195:Drug Design; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / Q000037:antagonists & inhibitors*; D004926:Escherichia coli / Q000201:enzymology; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors*; D010647:Phenyl Ethers / Q000138:chemical synthesis / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000201:enzymology; D011485:Protein Binding; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000981:Antiprotozoal Agents; D029968:Escherichia coli Proteins; D010647:Phenyl Ethers; D015800:Protozoan Proteins; C031538:phenyl ether; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)