Discovery of rigid biphenyl <i>Plasmodium falciparum</i> DHFR inhibitors using a fragment linking strategy-Reference-Cited by-同舟云学术

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

Published:2023 Issue:9 Volume:14 Page:1755-1766
ISSN:2632-8682
Container-title:RSC Medicinal Chemistry
language:en
Short-container-title:RSC Med. Chem.

Author:

Hoarau Marie¹^ORCID,Sermmai Patpanat¹,Varatthan Thaveechai¹,Thiabma Ratthiya¹,Jantra Tararat¹,Rattanajak Roonglawan¹,Vitsupakorn Danoo¹,Vanichtanankul Jarunee¹,Saepua Siriporn¹,Yuthavong Yongyuth¹,Thongpanchang Chawanee¹^ORCID,Kamchonwongpaisan Sumalee¹

Affiliation:

1. National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency, Pathum Thani 12120, Thailand

Abstract

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.

Funder

National Science and Technology Development Agency

Publisher

Royal Society of Chemistry (RSC)

Subject

Organic Chemistry,Drug Discovery,Pharmaceutical Science,Pharmacology,Molecular Medicine,Biochemistry

Link

http://pubs.rsc.org/en/content/articlepdf/2023/MD/D3MD00242J

Reference20 articles.

1. Malarial dihydrofolate reductase as a paradigm for drug development against a resistance-compromised target

2. First‐in‐human clinical trial to assess the safety, tolerability and pharmacokinetics of P218, a novel candidate for malaria chemoprotection

3. Chemoprotective Antimalarial Activity of P218 against Plasmodium falciparum: A Randomized, Placebo-Controlled Volunteer Infection Study

4. Strategy for Extending Half-life in Drug Design and Its Significance

5. Development of 2,4-Diaminopyrimidines as Antimalarials Based on Inhibition of the S108N and C59R+S108N Mutants of Dihydrofolate Reductase from Pyrimethamine-Resistant Plasmodium falciparum

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