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Leishmaniasis pp 885-890 | Cite as

Effects of a Squalene-2,3-Epoxidase Inhibitor on Propagation and Sterol Biosynthesis of Leishmania Promastigotes and Amastigotes

  • David H. Beach
  • L. John Goad
  • Jonathan D. Berman
  • Thomas E. Ellenberger
  • Steven M. Beverley
  • George G. HolzJr.
Part of the NATO ASI Series book series (NSSA, volume 171)

Abstract

A new class of antimycotic agents, the allylamines, are fungistatic or fungicidal for many different pathogenic dermatophytes and yeasts. Their primary mode of action is the inhibition of microsomal squalene-2,3-epoxidase, with accumulation of squalene and loss of cellular ergosterol accompanied by inhibition of growth and reproduction1. Cessation of cell growth and loss of viability coincide with the accumulation of squalene in some species (e.g. Candida parapsilosis), while in others (Candida albicans) complete growth inhibition requires the total cessation of ergosterol synthesis and minimum cellular ergosterol content1. The allylamines also demonstrate selective toxicity. Terbinafine SF 86–327, which is being developed for oral administration against systemic fungal infections, has a negligible effect on the squalene-2,3-epoxidase of vertebrate cholesterol biosynthesis at concentrations greater than the maximal serum concentrations that have been recorded in vitro1.

Keywords

Cutaneous Leishmaniasis Free Sterol Candida Parapsilosis Sterol Biosynthesis Trypanosoma Brucei 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • David H. Beach
    • 1
  • L. John Goad
    • 2
  • Jonathan D. Berman
    • 3
  • Thomas E. Ellenberger
    • 4
  • Steven M. Beverley
    • 4
  • George G. HolzJr.
    • 1
  1. 1.Department of Microbiology and ImmunologyS.U.N.Y. Health Science Center at SyracuseSyracuseUSA
  2. 2.Department of BiochemistryUniversity of LiverpoolLiverpoolUK
  3. 3.Division of Experimental Therapeutics, Walter Reed ArmyInstitute of ResearchUSA
  4. 4.Department of Biological Chemistry and Molecular PharmacologyHarvard Medical SchoolBostonUSA

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