Cell-based optimization of novel benzamides as potential antimalarial leads

Academic Article

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Overview

authors

• Wu, T.
• Nagle, A.
• Sakata, T.
• Henson, K.
• Borboa, R.
• Chen, Z.
• Kuhen, K.
• Plouffe, D.
• Winzeler, Elizabeth
• Adrian, F.
• Tuntland, T.
• Chang, J.
• Simerson, S.
• Howard, S.
• Ek, J.
• Isbell, J.
• Deng, X. M.
• Gray, N. S.
• Tully, D. C.
• Chatterjee, A. K.

publication date

• December 2009

journal

• Bioorganic & Medicinal Chemistry Letters  Journal

abstract

• Screening our in-house compound collection using a cell based Plasmodium falciparum proliferation assay we discovered a known pan-kinase inhibitor scaffold as a hit. Further optimization of this series led us to a novel benzamide scaffold which was devoid of human kinase activity while retaining its antiplasmodial activity. The evolution of this compound series leading to optimized candidates with good cellular potency against multiple strains as well as decent in vivo profile is described in this Letter.

subject areas

• Animals
• Antimalarials
• Benzamides
• Directed Molecular Evolution
• Enzyme Inhibitors
• Humans
• Mice
• Phosphotransferases
• Plasmodium falciparum

Research

keywords

• Cellular assay
• Cyclic amines
• Kinase
• Malaria
• Pharmacokinetics
• Resistant strains

Identity

PubMed Central ID

• PMC3532596

International Standard Serial Number (ISSN)

• 0960-894X

Digital Object Identifier (DOI)

• 10.1016/j.bmcl.2009.10.050

PubMed ID

• 19879133

Additional Document Info

start page

• 6970

end page

• 6974

volume

• 19

issue

• 24