Reviving the malaria fight with “open innovation” after public disclosure of potential antimalarial leads by the pharmaceutical consortium is a great idea (C&EN, May 24, page 11). I truly thank them. This open innovation should provide new impetus to revisit some specific parasite targets such as the malaria CDK (cyclin-dependent kinases).
A few years ago, my group at Walter Reed Army Institute of Research published two articles showing a 3-D pharmacophore model for inhibition of a Plasmodium falciparum CDK (also known as Pfmrk) developed from a set of several structurally diverse kinase inhibitors with a wide range of activity (J. Med. Chem. 2004, 47, 5418; Expert Opin. Drug Discov. 2007, 2, 1115). Using the model as a search template for virtual screening of compound databases, we were able to discover 16 new potent Pfmrk inhibitors.
The compound (SJ000025081) shown in the C&EN article maps perfectly well onto our published pharmacophore model and predicts excellent antimalarial activity. Thus the model may be a useful tool for rapid selection of inhibitors for the malarial kinases.
Apurba K. Bhattacharjee
Silver Spring, Md.