A Holistic In-Silico Characterization of Mortalin (HSPA9) Inhibitors from Murraya koenigii and Pogostemon cablin for TP53 Reactivation in Breast Cancer
DOI:
https://doi.org/10.48048/tis.2026.13664Keywords:
Breast cancer, Mortalin, TP53, Murraya koenigii, Pogostemon cablin, 8,8’’-Biskoenigine, Apigenin derivativeAbstract
Breast cancer, a leading cause of cancer-related deaths, is characterized by therapeutic challenges, including side effects and drug resistance. The interaction between mortalin (HSPA9) and p53, a tumor suppressor, is known to play a crucial role in cancer progression, as mortalin sequesters p53 and inhibits its tumor-suppressive functions. This study evaluated the potential of bioactive compounds from Murraya koenigii and Pogostemon cablin as novel therapeutic agents for breast cancer through targeting the mortalin-p53 interaction. An in silico approach combining network pharmacology, molecular docking, and molecular dynamics was employed to identify potential inhibitors of this interaction. The study identified two promising candidates: 8,8’’-biskoenigine (CID: 12967046) from M. koenigii and apigenin 7-(6’’-p-coumarylglucoside) (CID: 44257826) from P. cablin. These compounds were screened for drug-likeness, pharmacokinetics, and binding affinity to mortalin. Molecular docking and dynamics simulations demonstrated stable binding interactions with mortalin, particularly with 8,8’’-biskoenigine (‒7,9 kcal/mol), which showed the strongest binding affinity and stability among the candidates. These findings highlight the potential of phytochemicals from M. koenigii and P. cablin as targeted breast cancer treatments by modulating the mortalin-p53 signaling axis. Further experimental validation is needed to confirm their efficacy in vitro and in vivo. This research offers a promising direction for the development of plant-based compounds as effective cancer therapeutics.
HIGHLIGHTS
- The first comprehensive in silico validation establishes that koenigii and P. cablin are potent mortalin inhibitors, unlocking p53-mediated breast cancer therapy.
- 8,8-Biskoenigine (CID 12967046) from Murraya koenigiishowed superior -7.9 kcal/mol affinity and 50-ns MD stability versus controls (mortaparib plus and embelin).
- Apigenin 7-(6”-p-coumarylglucoside (CID 44257826) from Pogostemon cablin emerged as a secondary lead with favorable interactions at key residues (Phe262, Asn221) and drug-like ADMET properties.
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