Design and synthesis of novel benzofurans as a new class of antifungal agents targeting fungal N-myristoyltransferase. Part 1

M Masubuchi; K Kawasaki; H Ebiike; Y Ikeda; S Tsujii; S Sogabe; T Fujii; K Sakata; Y Shiratori; Y Aoki; T Ohtsuka; N Shimma

doi:10.1016/s0960-894x(01)00319-5

Design and synthesis of novel benzofurans as a new class of antifungal agents targeting fungal N-myristoyltransferase. Part 1

Bioorg Med Chem Lett. 2001 Jul 23;11(14):1833-7. doi: 10.1016/s0960-894x(01)00319-5.

Authors

M Masubuchi¹, K Kawasaki, H Ebiike, Y Ikeda, S Tsujii, S Sogabe, T Fujii, K Sakata, Y Shiratori, Y Aoki, T Ohtsuka, N Shimma

Affiliation

¹ Nippon Roche Research Center, 200 Kajiwara, Kamakura, 247-8530, Kanagawa, Japan.

PMID: 11459642
DOI: 10.1016/s0960-894x(01)00319-5

Abstract

Potent and selective Candida albicans N-myristoyltransferase (CaNmt) inhibitors have been identified through optimization of a lead compound 1 discovered by random screening. The inhibitor design is based on the crystal structure of the CaNmt complex with compound (S)-3 and structure-activity relationships (SARs) have been clarified. Modification of the C-4 side chain of 1 has led to the discovery of a potent and selective CaNmt inhibitor 11 (RO-09-4609), which exhibits antifungal activity against C. albicans in vitro.

MeSH terms

Acyltransferases / drug effects*
Antifungal Agents / chemical synthesis*
Antifungal Agents / pharmacology*
Benzofurans / chemical synthesis*
Benzofurans / pharmacology*
Candida albicans / drug effects
Candida albicans / enzymology*
Crystallography, X-Ray
Drug Design
Humans
Inhibitory Concentration 50
Receptors, Adrenergic, beta / drug effects
Species Specificity
Structure-Activity Relationship

Substances

Antifungal Agents
Benzofurans
Receptors, Adrenergic, beta
Acyltransferases
glycylpeptide N-tetradecanoyltransferase