doiSerbia

New 9-aminoacridine derivatives as inhibitors of Botulinum neurotoxins and P. falciparum malaria

Tot Mikloš (Faculty of Chemistry, Belgrade)
Opsenica Dejan M. (Institute of Chemistry, Technology, and Metallurgy, Belgrade)
Mitrić Milena (Faculty of Chemistry, Belgrade)
Burnett James C. (SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, USA)
Gomba Laura (United States Army Medical Research Institute of Infectious Diseases, Department of Bacteriology, Frederick, USA)
Bavari Sina (United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, USA)
Šolaja Bogdan A. (Faculty of Chemistry, Belgrade)

Steroidal and adamantane aminoacridine derivatives were prepared and tested as both botulinum neurotoxin (BoNT) inhibitors and antimalarials. Steroid-bound acridines provided good potency against both the BoNT/A and BoNT/B light chains (LCs). The observed inhibition of the BoNT/B LC by ca. 50% is the highest attained inhibitory activity against this serotype by acridine-based compounds to date. With respect to antimalarial activity, adamantane acridines were the most potent derivatives (IC50 = 6-9 nM, SI > 326), indicating that an adamantyl group is a better carries than a steroidal motif for this indication.

Keywords: antiviral, BoNT/A, BoNT/B, antimalarial, aminoacridine

Projekat Ministarstva nauke Republike Srbije, br. 172008