diphenyl urea derivatives as inhibitors of transketolase a structure-based virtual screening二苯脲衍生品作为虚拟筛选小转酮醇酶的抑制剂.pdfVIP

Diphenyl Urea Derivatives as Inhibitors of Transketolase: A Structure-Based Virtual Screening 1.¤ ´ 2. 2 1 Cristian Obiol-Pardo , Gema Alcarraz-Vizan , Marta Cascante *, Jaime Rubio-Martinez * ´ ´ ´ ´ ` 1 Departamento de Quımica Fısica, Facultat de Quımica, Universitat de Barcelona and Institut de Recerca en Quımica Teorica i Computacional (IQTCUB), Barcelona, Spain, ´ 2 Departamento de Bioquımica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona and Institute of Biomedicine at Universitat de Barcelona (IBUB), Barcelona, Spain Abstract Transketolase is an enzyme involved in a critical step of the non-oxidative branch of the pentose phosphate pathway whose inhibition could lead to new anticancer drugs. Here, we report new human transketolase inhibitors, based on the phenyl urea scaffold, found by applying structure-based virtual screening. These inhibitors are designed to cover a hot spot in the dimerization interface of the homodimer of the enzyme, providing for the first time compounds with a suggested novel binding mode not based on mimicking the thiamine pyrophosphate cofactor. ´ Citation: Obiol-Pardo C, Alcarraz-Vizan G, Cascante M, Rubio-Martinez J (2012) Diphenyl Urea Derivatives as Inhibitors of Transketolase: A Structure-Based Virtual Screening. PLoS ONE 7(3): e32276. doi:10.1371/journal.pone.0032276 ´ Editor: Ramon Campos-Olivas, Spanish National Cancer Center, Spain Received September 27, 2011; Accept