1,4-Benzothiazine and 1,4-benzoxazine Imidazole Derivatives With Antifungal Activity: A Docking Study

Bioorg Med Chem. 2002 Nov;10(11):3415-23. doi: 10.1016/s0968-0896(02)00263-8.

Abstract

We have recently described the synthesis and antifungal activity of a series of 1,4-benzothiazine and 1,4-benzoxazine imidazole derivatives that mainly showed in vivo activity against a murine experimental model of candidiasis but that very often lacked in vitro activity. Here, we report a docking study of a representative set of our molecules in a 3D model of CYP51 of Candida albicans (CA-CYP51). The model was constructed on the basis of the sequence homology relationship with the recently reported crystal structure of the CYP51 of Mycobacterium tuberculosis (MT- CYP51).

MeSH terms

  • Amino Acid Sequence
  • Antifungal Agents / chemical synthesis*
  • Antifungal Agents / pharmacology*
  • Bacterial Proteins / antagonists & inhibitors
  • Bacterial Proteins / metabolism
  • Candida albicans / drug effects
  • Candida albicans / enzymology
  • Cytochrome P-450 Enzyme Inhibitors
  • Cytochrome P-450 Enzyme System / metabolism
  • Enzyme Inhibitors / pharmacology
  • Fungal Proteins*
  • Fungi / drug effects*
  • Imidazoles / chemical synthesis*
  • Imidazoles / pharmacology*
  • Isomerism
  • Models, Biological
  • Models, Molecular
  • Molecular Conformation
  • Molecular Sequence Data
  • Mycobacterium / drug effects
  • Mycobacterium / enzymology
  • Sequence Homology
  • Thiazines / chemical synthesis*
  • Thiazines / pharmacology*

Substances

  • 1,4-benzothiazine
  • Antifungal Agents
  • Bacterial Proteins
  • Cytochrome P-450 Enzyme Inhibitors
  • Enzyme Inhibitors
  • Fungal Proteins
  • Imidazoles
  • Thiazines
  • cytochrome P-450 CYP51, Candida albicans
  • Cytochrome P-450 Enzyme System