1. Novel diphenyl ethers: design, docking studies, synthesis and inhibition of enoyl ACP reductase of Plasmodium falciparum and Escherichia coli.
- Author
-
Chhibber M, Kumar G, Parasuraman P, Ramya TN, Surolia N, and Surolia A
- Subjects
- Animals, Anti-Bacterial Agents pharmacology, Antiprotozoal Agents pharmacology, Computer Simulation, Drug Design, Escherichia coli enzymology, Phenyl Ethers chemical synthesis, Plasmodium falciparum enzymology, Protein Binding, Structure-Activity Relationship, Anti-Bacterial Agents chemical synthesis, Antiprotozoal Agents chemical synthesis, Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) antagonists & inhibitors, Escherichia coli Proteins antagonists & inhibitors, Phenyl Ethers pharmacology, Protozoan Proteins antagonists & inhibitors
- 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.
- Published
- 2006
- Full Text
- View/download PDF