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Peer-reviewedCC BY 4.0Molecules

Integrated Biochemical and Computational Evaluation of Bis-Imidazolium Derivatives 3e–3g in Cholinesterase and HIV-1 Reverse Transcriptase Assays

  • Edanur Altuntas1,2
  • Aleyna Nalcaoglu Senocak1
  • Yasemin Ünver3
  • Halil Ibrahim Guler1
  1. 1Department of Molecular Biology and Genetics, Faculty of Science, Karadeniz Technical University, Trabzon 61080, Turkey
  2. 2Department of Molecular Biology and Genetics, Graduate Institute of Natural and Applied Sciences, Karadeniz Technical University, Trabzon 61080, Turkey
  3. 3Department of Chemistry, Faculty of Science, Karadeniz Technical University, Trabzon 61080, Turkey
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Abstract

Bis-imidazolium derivatives (3e, 3f, 3g) were evaluated for their inhibitory activity against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) using colorimetric assays and molecular docking. For the HIV-1 RT–3e complex, a 100 ns molecular dynamics (MD) simulation and Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) analysis were performed. Compound 3e emerged as the most active derivative, showing the lowest half-maximal inhibitory concentration (IC50) values: 13.36 µg/mL for AChE, 4.95 µg/mL for BChE, and 50.44 µg/mL for HIV-1 RT. Nevirapine produced 95.33% RT inhibition at 20 µM. Redocking validated the binding poses with root-mean-square deviation (RMSD) values below 2.0 Å, though docking scores lacked consistent correlation with experimental activity rankings. In the MD trajectory, 3e remained stable within the RT binding pocket, yielding an MM/GBSA energy of −51.04 ± 8.39 kcal/mol. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions indicated low gastrointestinal absorption, no blood–brain barrier permeation, and a high-confidence human ether-à-go-go-related gene (hERG) potassium channel blockade alert. These findings highlight 3e for further optimization.

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Cite

BibTeXRIS
BibTeX
@article{altuntas2026integrated,
  title = {{Integrated Biochemical and Computational Evaluation of Bis-Imidazolium Derivatives 3e–3g in Cholinesterase and HIV-1 Reverse Transcriptase Assays}},
  author = {Edanur Altuntas and Aleyna Nalcaoglu Senocak and Yasemin Ünver and Halil Ibrahim Guler},
  journal = {Molecules},
  year = {2026},
  month = nov,
  doi = {10.3390/molecules31214006},
  url = {https://www.mdpi.com/1420-3049/31/21/4006},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Integrated Biochemical and Computational Evaluation of Bis-Imidazolium Derivatives 3e–3g in Cholinesterase and HIV-1 Reverse Transcriptase Assays
AU  - Edanur Altuntas
AU  - Aleyna Nalcaoglu Senocak
AU  - Yasemin Ünver
AU  - Halil Ibrahim Guler
PY  - 2026
DA  - 2026/11/06
JO  - Molecules
DO  - 10.3390/molecules31214006
UR  - https://www.mdpi.com/1420-3049/31/21/4006
AB  - Bis-imidazolium derivatives (3e, 3f, 3g) were evaluated for their inhibitory activity against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) using colorimetric assays and molecular docking. For the HIV-1 RT–3e complex, a 100 ns molecular dynamics (MD) simulation and Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) analysis were performed. Compound 3e emerged as the most active derivative, showing the lowest half-maximal inhibitory concentration (IC50) values: 13.36 µg/mL for AChE, 4.95 µg/mL for BChE, and 50.44 µg/mL for HIV-1 RT. Nevirapine produced 95.33% RT inhibition at 20 µM. Redocking validated the binding poses with root-mean-square deviation (RMSD) values below 2.0 Å, though docking scores lacked consistent correlation with experimental activity rankings. In the MD trajectory, 3e remained stable within the RT binding pocket, yielding an MM/GBSA energy of −51.04 ± 8.39 kcal/mol. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions indicated low gastrointestinal absorption, no blood–brain barrier permeation, and a high-confidence human ether-à-go-go-related gene (hERG) potassium channel blockade alert. These findings highlight 3e for further optimization.
SN  - 1420-3049
ER  -