Harnessing Phytochemistry to Combat Indoleamine 2,3-dioxygenase 1 and Tryptophan 2,3-dioxygenase 2 in Restoring Tryptophan Homeostasis in Ovarian Cancer

Dysregulation of tryptophan metabolism activates Kynurenine (KYN), which facilitates tumor immune escape and ovarian cancer progression frequently results in high mortality due to delayed diagnosis. Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase 2 (TDO2) enzymes are primarily responsible for dysregulation in tryptophan metabolism. It was well understood that KYN became life-threatening, causing a cancerous condition. Recently, the urge has been satisfied with potential phytochemicals. Phytochemicals of Taxus baccata, Nelumbo nucifera, Saraca asoca, Trichosanthes cucumerina, Aracauria columnaris and Hymenocallis littoralis were chosen to target kynurenine activation. The molecular docking analysis of IDO1 and TDO2 with 368 phytochemicals reveals higher binding energy for Hinokiflavone, Hippeastrine, Campesterol, Clionasterol, [Formula: see text]-sitosterol, Violaxanthin, [Formula: see text]-amyrin and [Formula: see text]-carotene compounds, which were further analyzed to determine the pharmacokinetic properties and toxicity of hit compounds. Density functional theory (DFT) analysis was performed to determine the electronic effect of hit compounds, resulting in sturdy stability for Campesterol, Clionasterol and [Formula: see text]-sitosterol. Molecular dynamic simulation of protein–ligand complexes was further confirmed by the Desmond module V3 of Schrödinger software investigating phytochemicals possessing pharmacological effects with higher binding stability, promising a strategic approach to synthesizing phytochemicals encapsulated nanocarriers for drug delivery to combat tryptophan loss. This in silico approach portrays the interaction of beneficiary phytochemicals with IDO1 and TDO2 in ovarian cancer, restoring the tryptophan homeostasis, thus expanding the scope for in vitro and in vivo studies and hastening drug discovery and delivery.