In silico screening of Moringa oleifera derived bioactive compounds targeting FOXO1 and PTEN in oral cancer

Oral cancer (OC) remains a significant global health burden due to the high recurrence rates after conventional treatment. Medicinal plants have provided therapeutic leads for cancer for centuries and Moringa oleifera (MO) is rich in potentially anticancer phytochemicals. This in-silico study evaluated twenty MO-derived bioactive compounds against OC proliferation by targeting FOXO1 and PTEN, two key tumor suppressors regulating apoptosis, cell cycle, and PI3K/AKT signaling. Loss of FOXO1 and inactivation of PTEN contribute to oral carcinogenesis, therapeutic resistance, and poor prognosis, making them rational therapeutic targets. The ADMET properties were predicted with SwissADME and ProTox-III and the binding affinities of the MO compounds to FOXO1 and PTEN were evaluated with molecular docking in comparison with 5’-Fluorouracil (5’-FU) as reference. FOXO1 showed the best affinity for Pterygospermin (-8.6 kcal/mol) followed by Isorhamnetin (-8.3), Quercetin (-8.1), Kaempferol (-8.1), Myricetin (-8.1) and Apigenin (-8.0), all significantly better than 5’-FU (-5.0). For PTEN, the highest score was for Apigenin (-7.9), followed by Myricetin (-7.7), Kaempferol (-7.6), Quercetin (-7.4) and Isorhamnetin (-7.4), compared to 5-FU (-4.9). Toxicity predictions indicated that some compounds may have the risks of being carcinogenic, mutagenic or immunotoxic. However, Pterygospermin, Apigenin and several others showed no predicted toxicity with favorable drug-likeness, pharmacokinetics and adequate predicted oral bioavailability. These results indicate that MO-derived compounds are promising candidates for individualized therapy of OC. But the results are of predicted binding, not verified activation. Molecular dynamics, in-vitro, in-vivo and pre-clinical validation are required to confirm efficacy, safety and mechanism.