Structure-based design, synthesis and preliminary evaluation of selective inhibitors of dihydrofolate reductase from Mycobacterium tuberculosis

MHRI El-Hamamsy, AW Smith, AS Thompson…

Index: El-Hamamsy, Mervat H.R.I.; Smith, Anthony W.; Thompson, Andrew S.; Threadgill, Michael D. Bioorganic and Medicinal Chemistry, 2007 , vol. 15, # 13 p. 4552 - 4576

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Citation Number: 51

Abstract

Tuberculosis is an increasing threat, owing to the spread of AIDS and to the development of resistance of the causative organism, Mycobacterium tuberculosis, to the currently available drugs. Dihydrofolate reductase (DHFR) is an important enzyme of the folate cycle; inhibition of DHFR inhibits growth and causes cell death. The crystal structure of M. tuberculosis DHFR revealed a glycerol tightly bound close to the binding site for the substrate ...