Identification and In-Vitro ADME Assessment of a Series of Novel Anti-Malarial Agents Suitable for Hit-to-Lead Chemistry

Chris D Edlin; Garreth Morgans; Susan Winks; Sandra Duffy; Vicky M Avery; Sergio Wittlin; David Waterson; Jeremy Burrows; Justin Bryans

doi:10.1021/ml300091c

Identification and In-Vitro ADME Assessment of a Series of Novel Anti-Malarial Agents Suitable for Hit-to-Lead Chemistry

ACS Med Chem Lett. 2012 May 28;3(7):570-3. doi: 10.1021/ml300091c. eCollection 2012 Jul 12.

Authors

Chris D Edlin¹, Garreth Morgans¹, Susan Winks¹, Sandra Duffy², Vicky M Avery², Sergio Wittlin³, David Waterson⁴, Jeremy Burrows⁴, Justin Bryans⁵

Affiliations

¹ iThemba Pharmaceuticals , P.O. Box 21, Modderfontein 1645, South Africa.
² Discovery Biology Institute, Griffith University , Brisbane, Queensland 4111, Australia.
³ Swiss Tropical and Public Health Institute , Socinstrasse 57, 4002 Basel, Switzerland.
⁴ Medicines for Malaria Venture , ICCRoute de Pre-Bois 20, P.O. Box 1826, 1215 Geneva, Switzerland.
⁵ Medical Research Council Technology , 1-3 Burtonhole Lane, Mill Hill, London, United Kingdom.

Abstract

Triage of a set of antimalaria hit compounds, identified through high throughput screening against the Chloroquine sensitive (3D7) and resistant (Dd2) parasite Plasmodium falciparum strains identified several novel chemotypes suitable for hit-to-lead chemistry investigation. The set was further refined through investigation of their in vitro ADME properties, which identified templates with good potential to be developed further as antimalarial agents. One example was profiled in an in vivo murine Plasmodium berghei model of malaria infection.

Keywords: Plasmodium falciparum; Screening; hit-to-lead chemistry; phenotypic screening.