Research Article
Molecular Modelling Applied to the Computer-aided Design of Inhibitors of Mycobacterium Tuberculosis Aminoglycoside Acetyltransferase (Eis) to Combat Kanamycin Resistance
Bamba Ibrahim,
Kouadja Rika Justin,
Mousse Logbo Mathias,
Soro Issouf,
Niare Adama*,
Megnassan Eugene
Issue:
Volume 10, Issue 1, June 2026
Pages:
1-21
Received:
8 May 2026
Accepted:
19 May 2026
Published:
30 May 2026
Abstract: Globally, tuberculosis continues to be a primary cause of death resulting from infectious diseases. The rise of resistant bacterial strains significantly undermines the effectiveness of current treatments. This study examines new sulfonamide derivatives (SULF) that target the Eis enzyme of Mycobacterium tuberculosis. This enzyme plays a direct role in kanamycin resistance. Three-dimensional models of the Eis-SULF complexes were generated from the reference crystal structure (PDB: 5IV0). These complexes were used to construct a test set of thirteen compounds with known experimental activities and an external validation set of four additional compounds. Active conformations were identified using energy-based QSAR modeling. The gas-phase model exhibits an R² coefficient of 0.96. Cross-validation of the gas-phase model yields an R²cv value of 0.95. The standard error of the gas-phase model is 0.28. The model in a solvated environment shows an R² value of 0.97. Cross-validation in a solvated environment yields an R²cv of 0.96. The standard error in a solvated environment is 0.24. A virtual library of sulfonamides was then constructed. The screening was based on Lipinski’s rules and the PH4 model. The PH4 model has an R² value of 0.91. The standard error of the PH4 model is 0.45. Sixty-five compounds show potential for oral bioavailability. The most promising complexes were studied using molecular dynamics. This analysis assesses the stability of ligands in the active site. The MM/GBSA approach was employed to calculate the binding free energies of the complexes. These calculations confirm a high affinity for the Eis enzyme. This integrated approach proposes promising new inhibitors against drug-resistant tuberculosis.
Abstract: Globally, tuberculosis continues to be a primary cause of death resulting from infectious diseases. The rise of resistant bacterial strains significantly undermines the effectiveness of current treatments. This study examines new sulfonamide derivatives (SULF) that target the Eis enzyme of Mycobacterium tuberculosis. This enzyme plays a direct role...
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Communication
A Quantum-Biochemical Model of AA-5-HT-Induced Cytotoxicity in HL-60 Cells via FAAH Inhibition and Cannabinoid Receptor–Mediated Signal Interference
Atakuru Dradre Paulin*
Issue:
Volume 10, Issue 1, June 2026
Pages:
22-27
Received:
23 April 2026
Accepted:
18 May 2026
Published:
21 October 2026
Abstract: Acute promyelocytic leukemia (APL) remains one of the most aggressive hematological malignancies, necessitating the discovery of novel therapeutic agents with improved efficacy and reduced toxicity. N-arachidonoyl-5-hydroxytryptamine (AA-5-HT), a hybrid indole–fatty acid amide compound isolated from Dialium corbisieri, has demonstrated potent cytotoxic activity in HL-60 leukemia cells, characterized by G1 phase cell cycle arrest at low micromolar concentrations (2.3µM). Despite these promising findings, its mechanism of action remains incompletely understood. Here, we propose a quantum-biochemical hypothesis integrating molecular pharmacology with principles derived from quantum theory to explain AA-5-HT-induced cytotoxicity. We hypothesize that AA-5-HT inhibits fatty acid amide hydrolase (FAAH), leading to accumulation of anandamide (AEA), which in turn activates Gi/o-coupled cannabinoid receptors (CB1/CB2). This activation suppresses the PI3K/AKT signaling pathway, resulting in decreased AKT phosphorylation, upregulation of cyclin-dependent kinase inhibitors (p21, p27), reduced retinoblastoma protein phosphorylation, and consequent G1 arrest. From a quantum-biochemical perspective, AA-5-HT acts as a perturbator that shifts intracellular signaling probabilities, promoting destructive interference of pro-survival pathways and stabilizing a non-proliferative cellular state. This framework provides a novel conceptual model for understanding anticancer mechanisms and suggests new experimental directions for validating AA-5-HT as a therapeutic candidate.
Abstract: Acute promyelocytic leukemia (APL) remains one of the most aggressive hematological malignancies, necessitating the discovery of novel therapeutic agents with improved efficacy and reduced toxicity. N-arachidonoyl-5-hydroxytryptamine (AA-5-HT), a hybrid indole–fatty acid amide compound isolated from Dialium corbisieri, has demonstrated potent cytot...
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