Computational Analysis of Azole Derivatives Targeting the PI3K/AKT/mTOR Pathway With In Vitro Cytotoxicity and Autophagy Evaluation.
2/5 보강
OpenAlex 토픽 ·
PI3K/AKT/mTOR signaling in cancer
Autophagy in Disease and Therapy
Synthesis and biological activity
This study aims to identify potential azole-derived inhibitors targeting the PI3K/AKT/mTOR signaling pathway involved in autophagy regulation and cancer progression.
APA
Rathika Regurajan, Merlin Sobia Poomani, et al. (2026). Computational Analysis of Azole Derivatives Targeting the PI3K/AKT/mTOR Pathway With In Vitro Cytotoxicity and Autophagy Evaluation.. Journal of biochemical and molecular toxicology, 40(5), e70859. https://doi.org/10.1002/jbt.70859
MLA
Rathika Regurajan, et al.. "Computational Analysis of Azole Derivatives Targeting the PI3K/AKT/mTOR Pathway With In Vitro Cytotoxicity and Autophagy Evaluation.." Journal of biochemical and molecular toxicology, vol. 40, no. 5, 2026, pp. e70859.
PMID
42021531 ↗
Abstract 한글 요약
This study aims to identify potential azole-derived inhibitors targeting the PI3K/AKT/mTOR signaling pathway involved in autophagy regulation and cancer progression. A structure-based virtual screening approach was employed using molecular docking, molecular dynamics (MD) simulations, and free energy calculations (MMGBSA and MMPBSA). The pharmacokinetic profiles and toxicity of lead compounds were assessed using ADMET analysis. In vitro validation was performed using MTT and MDC staining assays on MDA-MB-231 breast cancer cells.Among the screened compounds, KR4 demonstrated strong binding affinity towards all three kinases (-8.289, -5.222, and -6.331 kcal/mol) respectively with favorable pharmacokinetic properties. MD simulation confirmed the stability of the KR4-protein complexes, while post-MD MMPBSA analysis validated the binding energetics. In vitro studies revealed dose-dependent cytotoxicity of KR4 (IC₅₀ ≈ 39 µM) and induction of autophagy in treated cells. The integration of in silico and in vitro approaches highlights KR4 as a promising multi-target inhibitor of the PI3K/AKT/mTOR pathway with potential anti-cancer properties. These findings support further exploration of KR4 for therapeutic development.
🏷️ 키워드 / MeSH 📖 같은 키워드 OA만
- TOR Serine-Threonine Kinases
- Humans
- Proto-Oncogene Proteins c-akt
- Autophagy
- Phosphatidylinositol 3-Kinases
- Molecular Docking Simulation
- Signal Transduction
- Cell Line
- Tumor
- Molecular Dynamics Simulation
- Azoles
- Antineoplastic Agents
- AKT and mTOR
- PI3K
- autophagy
- azole derivatives
- binding energy
- receptor
🏷️ 같은 키워드 · 무료전문 — 이 논문 MeSH/keyword 기반
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