Antiplasmodial and antitumor activity of dihydroartemisinin analogs derived via the aza-Michael addition reaction

Tzu-Shean Feng; Eric M Guantai; Margo J Nell; Constance E J van Rensburg; Heinrich C Hoppe; Kelly Chibale

doi:10.1016/j.bmcl.2011.03.090

Antiplasmodial and antitumor activity of dihydroartemisinin analogs derived via the aza-Michael addition reaction

Bioorg Med Chem Lett. 2011 May 15;21(10):2882-6. doi: 10.1016/j.bmcl.2011.03.090. Epub 2011 Mar 30.

Authors

Tzu-Shean Feng¹, Eric M Guantai, Margo J Nell, Constance E J van Rensburg, Heinrich C Hoppe, Kelly Chibale

Affiliation

¹ Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa.

PMID: 21489789
DOI: 10.1016/j.bmcl.2011.03.090

Abstract

A series of dihydroartemisinin derivatives were synthesized via an aza-Michael addition reaction to a dihydroartemisinin-based acrylate and were evaluated for antiplasmodial and antitumor activity. The target compounds showed excellent antiplasmodial activity, with dihydroartemisinin derivatives 5, 7, 9 and 13 exhibiting IC(50) values of ≤10 nM against both D10 and Dd2 strains of Plasmodium falciparum. Derivative 4d was the most active against the HeLa cancer cell line, with an IC(50) of 0.37 μM and the highest tumor specificity.

Publication types

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

MeSH terms

Antimalarials / chemical synthesis*
Antimalarials / chemistry
Antimalarials / pharmacology*
Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Artemisinins / chemical synthesis*
Artemisinins / chemistry
Artemisinins / pharmacology*
Aza Compounds / chemistry
Cell Line, Tumor
Cell Survival / drug effects
HeLa Cells
Humans
Molecular Structure
Plasmodium falciparum / drug effects*

Substances

Antimalarials
Antineoplastic Agents
Artemisinins
Aza Compounds
artenimol