Published In

Journal of Medicinal Chemistry

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Pyrroles -- Synthesis, Tambjamines -- Antimalarial activity of, Ring formation (Chemistry), Chemical preparations industry


Synthesis and antimalarial activity of 94 novel bipyrrole tambjamines (TAs) and a library of B-ring functionalized tripyrrole prodiginines (PGs) against a panel of Plasmodium falciparum strains are described. The activity and structure–activity relationships demonstrate that the ring-C of PGs can be replaced by an alkylamine, providing for TAs with retained/enhanced potency. Furthermore, ring-B of PGs/TAs can be substituted with short alkyl substitutions at either 4-position (replacement of OMe) or 3- and 4-positions without impacting potency. Eight representative TAs and two PGs have been evaluated for antimalarial activity against multidrug-resistant P. yoelii in mice in the dose range of 5–100 mg/kg × 4 days by oral administration. The KAR425 TA offered greater efficacy than previously observed for any PG, providing 100% protection to malaria-infected mice until day 28 at doses of 25 and 50 mg/kg × 4 days, and was also curative in this model in a single oral dose (80 mg/kg). This study presents the first account of antimalarial activity in tambjamines.


Supporting Information

  • Molecular formula strings (XLSX) .
  • Structural characterization data and spectra (NMR, and HRMS)and all final compounds (PDF)

United States provisional patent application has been filed by Portland State University to protect the intellectual property described in this report. This work was authored as part of the Contributor's official duties as an Employee of the United States Government and is therefore a work of the United States Government. In accordance with 17 U.S.C. 105. This is the publisher’s final pdf. The version of record also available at: ACS Publications website.



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