Novel diphenyl ethers: Design, docking studies, synthesis and inhibition of enoyl ACP reductase of Plasmodium falciparum and Escherichia coli

• Published in: Bioorganic & medicinal chemistry Vol. 14; no. 23; pp. 8086 - 8098
• Main Authors: Chhibber, Manmohan, Kumar, Gyanendra, Parasuraman, Prasanna, Ramya, T.N.C., Surolia, Namita, Surolia, Avadhesha
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.12.2006; Elsevier Science
• Subjects: Animals; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiparasitic agents; Antiprotozoal Agents - chemical synthesis; Antiprotozoal Agents - pharmacology; Biological and medical sciences; Computer Simulation; Diphenyl ether; Docking; Drug Design; Enoyl ACP reductase; Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) - antagonists & inhibitors; Escherichia coli - enzymology; Escherichia coli Proteins - antagonists & inhibitors; General aspects; Medical sciences; Pharmacology. Drug treatments; Phenyl Ethers - chemical synthesis; Phenyl Ethers - pharmacology; Plasmodium falciparum - enzymology; Plasmodium falcisparum; Protein Binding; Protozoan Proteins - antagonists & inhibitors; Structure-Activity Relationship; EcENR; vdw volume; Enoyl ACP reductase; PfENR; Diphenyl ether; ENR; FAS; Docking; Plasmodium falcisparum; Antimalarial; Escherichia coli; Enoyl-[acyl-carrier-protein] reductase (NADH); Modeling; Antimicrobial agent; Antiprotozoal agent; Plasmodium falciparum; Structure activity relation; Chlorine Organic compounds; Molecular model; Bacteria; Aromatic compound; Chemical synthesis; Enterobacteriaceae; Protozoa; Apicomplexa; Ether; Enzyme; Prediction; Enzyme inhibitor; In vitro; Genetic algorithm; Binding energy; Phenols; Parasiticide; Oxidoreductases; Triclosan; Thermodynamic properties
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2006.07.034

Novel diphenyl ether compounds inhibit the enoyl-acyl carrier protein reductase of Plasmodium falciparum and Escherichia coli. Some of these compounds also show potency against in vitro cultures of the two pathogens. 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.