Bradley Research Sept 2007

The synthesis of anti-malarial and anti-tumor agents using the Ugi

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Jean-Claude Bradley

September 26, 2007

Research Mini-Symposium at Drexel University

The Malaria Problem

• Over 300 million people a year infected

• Over 1 million deaths per year

• Increasing resistance to existing drugs means there is a pressing need for new anti-malarial agents

The Ugi Reaction

Virtual library of 500K Ugi products

Some Ugi products predicted to bind to malarial enzymes

Enoyl reductase

Falcipain-2

• Breaks down hemoglobin

• Collaboration with the Rosenthal group at UCSF

Open Primary Research in Drug Design using Web2.0 tools

(blogs, wikis, Second Life, mailing lists)

Docking

Synthesis

Testing

Rajarshi GuhaIndiana U

JC BradleyDrexel U

Phil RosenthalUCSF

(malaria)

Dan ZaharevitzNCI

(tumors)

Tsu-Soo TanNanyang Poly.

Closing the Loop

• Wired Magazine• Nature blogs• C&E News• Cell• Per Contra• Assignment Zero• NPR Marketplace• Chemistry Central• 3 Quarks Daily

The UsefulChem Project and Open Notebook Science in the media

The public wiki is the lab notebook Each Experiment on a Wiki Page

Tracking Experiment Edits(advisor’s comments in bold/italics)

Experiment History

Monitoring experimental progress

Third Party Time-Stamp on Experiment Versions

Graphical Mining of Data with JSpecView

usefulchem.wikispaces.com/Exp070 (48h 7 min)

usefulchem.blogspot.com

The blog as an integrative tool

How are people finding our experiments?

Molecules found by InChI

Comments from peers

Mailing List Facilitates inter-group collaboration

Telling the story of the failures

Mechanistic Studies of acid-catalyzed furfuryl group cleavage

What is the role of the amide as a leaving group?

Group present/past

• Khalid Mirza

• Rikesh Parikh

• Mitesh Shah

• Sean Gardner

• Jessica Colditz

• Dave Strumfels

• James Giammarco