Exploring the scope of new arylamino alcohol derivatives: Synthesis, antimalarial evaluation, toxicological studies, and target exploration
Keywords: 
Antimalarial
Antiplasmodial
Arylamino alcohol
Plasmepsin II enzyme
Hemozoin inhibition
Mannich reaction
Issue Date: 
2016
ISSN: 
2211-3207
Editorial note: 
This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).
Citation: 
Quiliano, M. (Miguel); Mendoza, A. (Adela); Fong, K. Y. (Kim); et al. "Exploring the scope of new arylamino alcohol derivatives: Synthesis, antimalarial evaluation, toxicological studies, and target exploration". International Journal for Parasitology: Drugs and Drug Resistance. 6 (3), 2016, 184 - 198
Abstract
Synthesis of new 1-aryl-3-substituted propanol derivatives followed by structure-activity relationship, in silico drug-likeness, cytotoxicity, genotoxicity, in silico metabolism, in silico pharmacophore modeling, and in vivo studies led to the identification of compounds 22 and 23 with significant in vitro antiplasmodial activity against drug sensitive (D6 IC50 0.19 mM) and multidrug resistant (FCR-3 IC50 0.40 mM and C235 IC50 0.28 mM) strains of Plasmodium falciparum. Adequate selectivity index and absence of genotoxicity was also observed. Notably, compound 22 displays excellent parasitemia reduction (98 ± 1%), and complete cure with all treated mice surviving through the entire period with no signs of toxicity. One important factor is the agreement between in vitro potency and in vivo studies. Target exploration was performed; this chemotype series exhibits an alternative antimalarial mechanism.

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