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Effect of Hydration on the Molecular Dynamics of Hydroxychloroquine Sulfate.

ABSTRACT: Chloroquine and its derivative hydroxychloroquine are primarily known as antimalaria drugs. Here, we investigate the influence of hydration water on the molecular dynamics in hydroxychloroquine sulfate, a commonly used solubilized drug form. When hydration, even at a low level, results in a disordered structure, as opposed to the highly ordered structure of dry hydroxychloroquine sulfate, the activation barriers for the rotation of methyl groups in the drug molecules become randomized and, on average, significantly reduced. The facilitated stochastic motions of the methyl groups may benefit the biomolecular activity due to the more efficient sampling of the energy landscape in the disordered hydration environment experienced by the drug molecules in vivo.

SUBMITTER: Mamontov E

PROVIDER: S-EPMC7423024 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Effect of Hydration on the Molecular Dynamics of Hydroxychloroquine Sulfate.

Mamontov Eugene E Cheng Yongqiang Y Daemen Luke L LL Keum Jong K JK Kolesnikov Alexander I AI Pajerowski Daniel D Podlesnyak Andrey A Ramirez-Cuesta Anibal J AJ Ryder Matthew R MR Stone Matthew B MB

ACS omega 20200810 33

Chloroquine and its derivative hydroxychloroquine are primarily known as antimalaria drugs. Here, we investigate the influence of hydration water on the molecular dynamics in hydroxychloroquine sulfate, a commonly used solubilized drug form. When hydration, even at a low level, results in a disordered structure, as opposed to the highly ordered structure of dry hydroxychloroquine sulfate, the activation barriers for the rotation of methyl groups in the drug molecules become randomized and, on av ...[more]

PMID: 32869009

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