A Holistic In-Silico Characterization of Mortalin (HSPA9) Inhibitors from Murraya koenigii and Pogostemon cablin for TP53 Reactivation in Breast Cancer

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, with mortalin sequestering p53 and inhibiting 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 possible 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 treatments for breast cancer 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.

Keywords: Breast cancer, Mortalin, TP53, Murraya koenigii, Pogostemon cablin, 8,8’’-Biskoenigine, Apigenin derivative