Synthesis, characterization, and cellular localization of a fluorescent probe of the antimalarial 8-aminoquinoline primaquine

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:27

Article

McQueen, Adonis¹  Blake, Lynn D.¹  Azhari, Ala³  Kemp, M. Trent¹  McGaha, Tommy W., Jr.³  Namelikonda, Niranjan²  Larsen, Randy W.²  Manetsch, Roman^2,4,5,6  Kyle, Dennis E.³ 

[1] Univ S Florida, Dept Mol Med, Morsani Coll Med, Tampa, FL USA

[2] Univ S Florida, Dept Chem, Coll Arts & Sci, Tampa, FL USA

[3] Univ S Florida, Coll Publ Hlth, Dept Global Hlth, Tampa, FL 33620 USA

[4] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA

[5] Northeastern Univ, Dept Pharmaceut Sci, Coll Sci, Boston, MA 02115 USA

[6] Northeastern Univ, Bouve Coll Hlth Sci, Boston, MA 02115 USA

关键词: Plasmodium falciparum;    Primaquine;    8-Aminoquinoline;    Fluorescent probe;    Malaria;   

DOI  :  10.1016/j.bmcl.2017.09.030

来源: Elsevier

【 摘 要 】

Primaquine (PQ) is the only commercially available drug that clears dormant liver stages of malaria and blocks transmission to mosquito vectors. Although an old drug, much remains to be known about the mechanism(s) of action. Herein we develop a fluorescent tagged PQ to discover cellular localization in the human malaria parasite, Plasmodium falciparum. Successful synthesis and characterization of a primaquine-coumarin fluorescent probe (PQCP) demonstrated potency equivalent to the parent drug and the probe was not cytotoxic to HepG2 carcinoma cells. Cellular localization was found primarily in the cytosol of the asexual erythrocytic and gametocyte stages of parasite development. (C) 2017 Elsevier Ltd. All rights reserved.

【 授权许可】

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