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Drug Repurposing to Inhibit Histamine N-Methyl Transferase
Elvia Mera Jiménez, Teresa Żołek, Paola Gabriela Hernández Perez, Rene Miranda Ruvalcaba, María Inés Nicolás-Vázquez, Maricarmen Hernández-Rodríguez. Molecules (Basel, Switzerland), 2023-01-06
Topic: Drug trials: efficacy and safety
Lower activity of the histaminergic system is associated with neurological disorders, including Alzheimer's disease (AD). Thus, the enhancement of histaminergic neurotransmission by inhibition of histamine N-methyl transferase (HNMT), which degrades histamine, appears as an important approach. For this purpose, rigid and flexible molecular docking studies of 185 FDA-approved drugs with the HNMT enzyme were carried out to select two compounds to perform molecular dynamics (MD) simulations to evaluate the binding free energies and stability of the enzyme-drug complexes. Finally, an HNMT inhibition assay was performed to corroborate their effect towards HNMT. Molecular docking studies with HNMT allowed the selection of dihydroergotamine and vilazodone since these molecules showed the lowest Gibbs free energy values. Analysis of the binding mode of vilazodone showed interactions with the binding pocket of HNMT with Glu28, Gln143, and Asn283. In contrast, dihydroergotamine binds to the HNMT active site in a different location, apparently because it is overall the more rigid ligand compared to flexible vilazodone. HNMT inhibitory activity for dihydroergotamine and vilazodone was corroborated (IC50 = 72.89 μM and 45.01 μM, respectively) by in vitro assays. Drug repurposing of HNMT was achieved by employing computational studies.
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APA 7th
Jiménez, E. M., Żołek, T., Perez, P. G. H., Ruvalcaba, R. M., Nicolás-Vázquez, M. I., & Hernández-Rodríguez, M. (2023). Drug Repurposing to Inhibit Histamine N-Methyl Transferase. Molecules (Basel, Switzerland). https://doi.org/10.3390/molecules28020576
Vancouver
Jiménez EM, Żołek T, Perez PGH, Ruvalcaba RM, Nicolás-Vázquez MI, Hernández-Rodríguez M. Drug Repurposing to Inhibit Histamine N-Methyl Transferase. Molecules (Basel, Switzerland). 2023. doi:10.3390/molecules28020576. PMID: 36677633.
BibTeX
@article{jimenez2023-36677633,
author = {Jiménez, Elvia Mera and Żołek, Teresa and Perez, Paola Gabriela Hernández and Ruvalcaba, Rene Miranda and Nicolás-Vázquez, María Inés and Hernández-Rodríguez, Maricarmen},
title = {{Drug Repurposing to Inhibit Histamine N-Methyl Transferase}},
journal = {Molecules (Basel, Switzerland)},
year = {2023},
doi = {10.3390/molecules28020576},
pmid = {36677633},
url = {https://doi.org/10.3390/molecules28020576}
}
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Key findings
- Lower activity of the histaminergic system is associated with neurological disorders, including Alzheimer's disease (AD).
- In contrast, dihydroergotamine binds to the HNMT active site in a different location, apparently because it is overall the more rigid ligand compared to flexible vilazodone.
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Study details
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 23 of the 56 points we could judge it on, which is 41 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Molecules (Basel, Switzerland)) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2023 — within 6 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 36677633) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 23 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 23 of the 56 points we could judge it on is 41 out of 100. |
| Total | 41 / 100 | — |
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