ELQ-300   Click here for help

GtoPdb Ligand ID: 10021

Synonyms: ELQ300
Antimalarial Ligand
Compound class: Synthetic organic
Comment: ELQ-300 is a late lead candidate from a novel class of 4(1H)-quinolone-based compounds with potent antimalarial activity [4]. The ELQs (endochin-like quinolones) are structural derivatives of endochin (PubChem CID 100474), which has potent antiplasmodial activity, but is highly metabolically unstable in mammals [1,6].

The Malaria tab on this ligand page provides additional curator comments of relevance to the Guide to MALARIA PHARMACOLOGY.
Click here for help
2D Structure
Click here for help
Click here for structure editor
Physico-chemical Properties
Click here for help
Hydrogen bond acceptors 1
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 60.55
Molecular weight 475.08
XLogP 8.16
No. Lipinski's rules broken 1
Click here for help
Canonical SMILES COc1cc2[nH]c(C)c(c(=O)c2cc1Cl)c1ccc(cc1)Oc1ccc(cc1)OC(F)(F)F
Isomeric SMILES COc1cc2[nH]c(C)c(c(=O)c2cc1Cl)c1ccc(cc1)Oc1ccc(cc1)OC(F)(F)F
InChI InChI=1S/C24H17ClF3NO4/c1-13-22(23(30)18-11-19(25)21(31-2)12-20(18)29-13)14-3-5-15(6-4-14)32-16-7-9-17(10-8-16)33-24(26,27)28/h3-12H,1-2H3,(H,29,30)
Guide to Malaria Pharmacology Comments
Preclinical testing has found ELQ-300 to be active against P. falciparum and P. vivax and with the potential for both the prevention and treatment of malaria [4]. However, further clinical development of ELQ-300 has been impeded by its physicochemical properties. Poor aqueous solubility and high crystallinity limit oral absorption of the higher doses required for a single-dose cure and to establish an acceptable therapeutic window. To address this challenge, a prodrug approach has been used to identify ELQ-300 prodrugs with improved physicochemical properties and the potential for clinical formulation [2-3].

Potential Target/Mechanism Of Action: ELQ-300 is an inhibitor of the Plasmodium mitochondrial cytochrome bc1 complex. It targets the highly divergent Qi-site and has a low resistance propensity compared to atovaquone, which targets the widely conserved Qo-site [5].