Facile Synthesis and Preliminary Structure-Activity Analysis of New Sulfonamides Against Trypanosoma brucei

Adel A Rashad; Amy J Jones; Vicky M Avery; Jonathan Baell; Paul A Keller

doi:10.1021/ml400487t

Facile Synthesis and Preliminary Structure-Activity Analysis of New Sulfonamides Against Trypanosoma brucei

ACS Med Chem Lett. 2014 Mar 10;5(5):496-500. doi: 10.1021/ml400487t. eCollection 2014 May 8.

Authors

Adel A Rashad¹, Amy J Jones², Vicky M Avery², Jonathan Baell³, Paul A Keller¹

Affiliations

¹ School of Chemistry, University of Wollongong , Wollongong 2522, Australia.
² Eskitis Institute for Drug Discovery, Griffith University , Brisbane Innovation Park, Don Young Road, Nathan 4111, Australia.
³ Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University , 381 Royal Parade, Parkville 3052, Australia.

Abstract

The high throughput screening of a library of over 87,000 drug-like compounds against the African sleeping sickness parasite resulted in the discovery of hits with a wide range of molecular diversity. We report here the medicinal chemistry development of one such hit, a tetrahydroisoquinoline disulfonamide, with the synthesis and testing of 26 derivatives against the trypanosome subspecies. Activities in the 2-4 μM range were revealed with a selectivity index suitable for further development.

Keywords: SAR; T. brucei; sulfonamides; tetrahydroquinoline.