MUSHROOM DERIVED COMPOUNDS UNVEILED NARINGIN AS A POTENTIAL MULTI-TARGETED ANTI-BREAST CANCER COMPOUND - AN IN-SILICO APPROACH

Objective: The study aimed to evaluate the multiple target effect of phytochemicals of mushroom against breast cancer using molecular docking and dynamics approach. Material and Method: In this study, the binding affinity of forty mushroom phytochemicals with various breast cancer proteins such as epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), topoisomerase IIα and topoisomerase IIβ were investigated by docking study using the PyRx tool. The selected receptors are highly cancer influencing and they were selected based on literature. Further molecular dynamics studies were also carried out to confirm the stability and conformation of the naringin-protein complex. In-silico ADMET studies were also carried out to confirm the pharmacokinetic properties and toxicity of the mushroom phytochemicals. Result and Discussion: From the results obtained, colossolactone G, antcin-A, and formipinioside had higher affinity to EGFR than normal neratinib. Furthermore, fomitoside K, naringin and antcin-A were found to have higher binding affinity than neratinib with HER2. Besides, ergone, naringin, and ergosterol showed higher binding affinity than doxorubicin during interactions with topoisomerase IIα. On the other hand, antrocin, ergosterol peroxide and naringin demonstrated higher binding affinity against topoisomerase IIβ than doxorubicin. Further molecular dynamics studies were also carried out to confirm the stability and conformation of the naringin-protein complex which revealed the best binding score against all the four tested enzymes. Overall, this study suggests naringin as the best ligand and may have great potential in breast cancer protein inhibitors development. To demonstrate their therapeutic promise against breast cancer, more in vitro and in vivo research might be required.