1. Genotoxic effects of the antimalarial drug lumefantrine in human lymphocytes in vitro and computational prediction of the mechanism associated with its interaction with DNA.
- Author
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de Lucca RM, Batista Júnior J, Fontes CJ, Bahia Mde O, and Bassi-Branco CL
- Subjects
- Adult, Antimalarials chemistry, Antimalarials toxicity, Cells, Cultured, Comet Assay, DNA chemistry, Ethanolamines metabolism, Female, Fluorenes metabolism, Humans, Lumefantrine, Male, Micronucleus Tests, Molecular Docking Simulation, DNA metabolism, Ethanolamines chemistry, Ethanolamines toxicity, Fluorenes chemistry, Fluorenes toxicity, Lymphocytes drug effects
- Abstract
Lumefantrine (LF) is an aryl-amino alcohol antimalarial drug used in artemisinin-based combination therapies against malaria worldwide. In this study, we investigated the genotoxic effects of LF in human lymphocytes in vitro, and the potential noncovalent interaction of LF with DNA using a 3D DNA-docking model. The number of DNA breaks and the frequency of nuclear buds (NBUDS) was significantly increased (P < 0.01 and P < 0. 05, respectively) at LF concentrations of 60, 80, and 100 µg/mL (LF60, LF80, and LF100, respectively). Frequency (‰) of micronuclei (MN) formation also increased after LF treatments. However, this was only significant for LF100 (P = 0.01) and LF80 (P = 0.001). LF did not affect the frequency of nucleoplasmic bridges (NPBs) (P = 0.12) or the nuclear division index (NDI) (P = 0.32). Computational analysis suggests that LF may interact noncovalently with DNA via the DNA minor groove surface with a predicted binding affinity energy of -7.2 kcal/mol and showing a favorable shape complementary to this groove. Our results suggest that LF has clastogenic effects in human lymphocytes in vitro due to noncovalent interaction with the minor groove of DNA., (© 2015 Wiley Periodicals, Inc.)
- Published
- 2015
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