Squaric acid/4-aminoquinoline conjugates: novel potent antiplasmodial agents.
We report the synthesis and structure-activity relationship (SAR) analysis of a series of hybrid compounds containing a squaric moiety conjugated with heterocyclic moieties from well-known antimalarials. This novel series of compounds presents improved antiplasmodial activity compared with the squaric derivatives described in our previous work. Three compounds, 8b (IC₅₀ = 99 nM), 8c (IC₅₀ = 95 nM), and 8d (IC₅₀ = 105 nM) had greater in vitro potency than chloroquine 1 (IC₅₀ = 140 nM) against chloroquine resistant Plasmodium falciparum. In addition, they were noncytotoxic against NIH 3T3 and Hek 293T cells.
Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon. Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
Carlos J A
CJ
Ribeiro
S Praveen
SP
Kumar
Jiri
J
Gut
Lídia M
LM
Gonçalves
Philip J
PJ
Rosenthal
Rui
R
Moreira
Maria M M
MM
Santos
D000634:Aminoquinolines / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003503:Cyclobutanes / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D041681:NIH 3T3 Cells; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000634:Aminoquinolines; D000962:Antimalarials; D003503:Cyclobutanes; C001920:4-aminoquinoline; C030042:squaric acid
4-Aminoquinoline; Antiplasmodial activity; Hybrid; Malaria; Squaramide