Synthesis and antimalarial activity of N-benzylated (N-arylcarbamoyl)alkylphosphonic acid derivatives

Christiana M Adeyemi; Faridoon; Michelle Isaacs; Dumisani Mnkandhla; Heinrich C Hoppe; Rui W M Krause; Perry T Kaye

doi:10.1016/j.bmc.2016.04.021

Synthesis and antimalarial activity of N-benzylated (N-arylcarbamoyl)alkylphosphonic acid derivatives

Bioorg Med Chem. 2016 Dec 1;24(23):6131-6138. doi: 10.1016/j.bmc.2016.04.021. Epub 2016 Apr 9.

Authors

Christiana M Adeyemi¹, Faridoon¹, Michelle Isaacs², Dumisani Mnkandhla², Heinrich C Hoppe³, Rui W M Krause⁴, Perry T Kaye⁵

Affiliations

¹ Department of Chemistry, Rhodes University, Grahamstown 6140, South Africa.
² Centre for Chemico- and Biomedicinal Research, Rhodes University, Grahamstown 6140, South Africa.
³ Department of Biochemistry and Microbiolgy, Rhodes University, Grahamstown 6140, South Africa; Centre for Chemico- and Biomedicinal Research, Rhodes University, Grahamstown 6140, South Africa.
⁴ Department of Chemistry, Rhodes University, Grahamstown 6140, South Africa; Centre for Chemico- and Biomedicinal Research, Rhodes University, Grahamstown 6140, South Africa.
⁵ Department of Chemistry, Rhodes University, Grahamstown 6140, South Africa; Centre for Chemico- and Biomedicinal Research, Rhodes University, Grahamstown 6140, South Africa. Electronic address: [email protected].

PMID: 27773366
DOI: 10.1016/j.bmc.2016.04.021

Abstract

A series of novel and readily accessible N-benzylated (N-arylcarbamoyl)alkylphosphonate esters and related compounds have been prepared as potential antimalarial agents. Bioassays reveal that some of these compounds exhibit promising activity against Plasmodium falciparum, and exhibit no significant growth inhibition of HeLa cells.

Keywords: Anti-malarial; Aryl and heteroaryl derivatives; N-Benzylated phosphonate esters; PfDXR.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aldose-Ketose Isomerases / antagonists & inhibitors
Amides / chemical synthesis
Amides / pharmacology*
Amides / toxicity
Antimalarials / chemical synthesis
Antimalarials / pharmacology*
Antimalarials / toxicity
Fosfomycin / analogs & derivatives
Fosfomycin / pharmacology
HeLa Cells
Humans
Organophosphonates / chemical synthesis
Organophosphonates / pharmacology*
Organophosphonates / toxicity
Plasmodium falciparum / drug effects
Structure-Activity Relationship

Substances

Amides
Antimalarials
Organophosphonates
Fosfomycin
3-(N-acetyl-N-hydroxy)aminopropylphosphonic acid
1-deoxy-D-xylulose 5-phosphate reductoisomerase
Aldose-Ketose Isomerases