Studies on the interaction of 2,4-dibromophenol with human hemoglobin using multi-spectroscopic, molecular docking and molecular dynamics techniques

Sharma, Monika; Farhat, Nabeela; Khan, Asad U.; Khan, Fahim Halim; Mahmood, Riaz

doi:10.1080/07391102.2023.2264975

Cited by 4 publications

(1 citation statement)

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“…In the HRP protein system, compounds KDS12025 and HTPEB were docked into the catalytic binding site, and the robustness of the docking protocol was verified through the successful re-docking of ferulic acid within 1.5 Å of the co-crystallized ligand pose. For Hb, multiple binding sites in the Hbα and Hbβ subunits of the Hb tetramer were explored, guided by prior published Hb-small molecule docking studies (50)(51)(52)(53)(54). The ligand binding energy (ΔGbind) for the top 5 docking poses was determined using the MM-GBSA method under the Generalized Born with Molecular Volume (GBMV) solvent model and additionally, in situ ligand minimization was included in the protocol, where all protein residues within 6 Å of the ligand were treated as flexible.…”

Section: Docking and Binding Energy Calculationsmentioning

confidence: 99%

Hemoglobin as a peroxidase and drug target for oxidative stress-related diseases

Won,

Lee,

Gotina

et al. 2024

Preprint

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Hemoglobin (Hb) is well-known for transporting oxygen in red blood cells within blood vessels. However, its role in the brain has been largely unknown. Here, we report that Hb, found in hippocampal astrocytes of both animal models and Alzheimer's disease (AD) patients, displays significant antioxidant effects through its H2O2-decomposing peroxidase activity. To counteract the harmful effects of aberrant H2O2-production in AD, we developed KDS12025, a BBB-permeable small molecule that effectively enhances the H2O2-decomposing activity of Hb by 100-fold, even at very low level of Hb. KDS12025 reduces in astrocytes and reverses memory impairment in AD models. Gene-silencing of Hbbeta abrogates the enhancing effect of KDS12025 in both culture and animal models of AD. We propose boosting Hb's peroxidase activity as a new therapeutic approach for AD treatment.

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