Parallel solution-phase synthesis of conformationally restricted congeners of pentamidine and evaluation of their antiplasmodial activities

  • J Med Chem. 2004 May 6;47(10):2700-5. doi: 10.1021/jm030545e.
Annie Mayence  1 ,  Jean Jacques Vanden Eynde ,  Fran M Krogstad ,  Donald J Krogstad ,  Melanie T Cushion ,  Tien L Huang
Affiliations
  • 1. College of Pharmacy, Division of Basic Pharmaceutical Sciences, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, Louisiana 70125, USA.
PMID: 15115412 DOI: 10.1021/jm030545e
Abstract

Conformationally restricted bisbenzamidines and related congeners have been synthesized and evaluated for activity against two Plasmodium falciparum strains. The most active compounds, bisbenzamidines linked by a 1,4-piperazinediyl core, had IC(50) values between 3 and 18 nM against both chloroquine-susceptible and -resistant parasites and IC(50) values for cytotoxicity greater than 5 microM, using the A549 human lung epithelial cell line. DNA binding affinity, as estimated by DeltaT(m), did not correlate with either antiparasite effects or cytotoxicity. Each of the active bisbenzamidines interfered with the formation of hemozoin in cell-free systems.