DOI: 10.1039/d3md00242j ISSN: 2632-8682

Discovery of rigid biphenyl Plasmodium falciparum DHFR inhibitors using a fragment linking strategy

Marie Hoarau, Patpanat Sermmai, Thaveechai Varatthan, Ratthiya Thiabma, Tararat Jantra, Roonglawan Rattanajak, Danoo Vitsupakorn, Jarunee Vanichtanankul, Siriporn Saepua, Yongyuth Yuthavong, Chawanee Thongpanchang, Sumalee Kamchonwongpaisan
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science
  • Pharmacology
  • Molecular Medicine
  • Biochemistry

The screen of a fragment library identified hydrophobic fragments binding to drug resistant PfDHFR active site. Lead design using fragment-linking strategy yielded compounds with nM antimalarial activity, no cytotoxicity and drug-like properties.

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