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

RSC medicinal chemistry（2023）

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摘要

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

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关键词

dhfr inhibitors,rigid biphenyl

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