Electron affinity and dipole moment of 1,2,4,5-tetraoxanes antimalarials and correlation with activity against Plasmodium falciparum

Antimalarial activity of 1,2,4,5-tetraoxanes is believed to be related to oxidation of heme by the peroxide group. This observation suggests that electron affinity of tetraoxanes is related to its activity. We have investigated the electron affinity of 20 tetraoxanes using quantum chemistry calculat...

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Bibliographic Details
Published inMedicinal chemistry research Vol. 23; no. 12; pp. 5197 - 5203
Main Authors de Paula, Mariane C., Valle, Marcelo S., Pliego, Josefredo R.
Format Journal Article
LanguageEnglish
Published New York Springer US 01.12.2014
Subjects
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cell Biology
Original Research
Pharmacology/Toxicology
Electron transfer
Antimalarial
Density functional theory
QSAR
Electron affinity
Artemisinin
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Summary:Antimalarial activity of 1,2,4,5-tetraoxanes is believed to be related to oxidation of heme by the peroxide group. This observation suggests that electron affinity of tetraoxanes is related to its activity. We have investigated the electron affinity of 20 tetraoxanes using quantum chemistry calculations at X3LYP/6-31(+)G(d) level and analyzed its correlation with activity. Other two parameters, dipole moment and log P , were also investigated. Using multi-linear regression, we have found that the electron affinity and the dipole moment have meaningful correlation with pIC 50 for K1 strain of Plasmodium falciparum , while log P is less important. Molecule 16 is out of the correlation. Docking studies suggest that the high activity of molecule 16 could be due to the intermolecular interaction between the amine group of molecule 16 and the carboxylic acid group of heme.
ISSN:1054-2523
1554-8120
DOI:10.1007/s00044-014-1088-8