<i>In Silico</i> Pharmacological Evaluation of <i>Azadirachta indica</i> Phytochemicals Targeting Thalassemia-Associated Genes and Proteins

Thalassemia is an inherited hemoglobin disease characterized by persistent anemia, oxidative and iron overload due to transfusion, creating severe clinical and economic issues in South Asia. The adverse effects and adverse effects of current treatment options highlight the need to have safer and multi-target options. In this study, a comprehensive in silico pharmacoinformatic methodology was applied to determine the therapeutic value of Azadirachta indica (Neem) phytochemicals on thalassemia-related targets. One hundred and five phytocompounds were shortlisted, and the number of those passing drug-likeness and ADMET filters evaluated at SwissADME, MolSoft (v6.8) and ADMETlab 3.0 was 350. The intersecting genes were predicted by target prediction with SwissTargetPrediction and functionally enriched with the help of DAVID (v6.8) and KEGG (v113.0). Significantly enriched pathways were Lipid and Atherosclerosis (Benjamini [Formula: see text] 0.0236), Apoptosis ([Formula: see text] 0.043) and Chemical Carcinogenesis ([Formula: see text] 0.00167). The central hub genes were TNF, TP53, PPARG, CYP3A44 and found by the network analysis with the help of STRING (v11.5) and Cytoscape (v3.10.0). Molecular docking was done using PyRx (v0.9.8) with AutoDock Vina (v1.2.3) being implemented. The highest affinity of the screened compounds was found to be Naringenin, with a binding energy of −9.8 kcal/mol (PDB ID: 1v04), and it was greater than that of Hydroxyurea (−8.9 kcal/mol), Deferiprone (−5.3 kcal/mol) and Deferasirox (−5.3 kcal/mol). Quercetin, Luteolin and Genistein had a good binding profile with the presence of stable hydrogen bonding and [Formula: see text]–[Formula: see text] interactions as illustrated in PyMOL (v2.5). This cumulative computational pipeline lays significant evidence that phytochemicals derived from Neem are prime multi-target lead compounds to use as adjuncts in the treatment of thalassemia. These findings require further confirmation through molecular dynamics simulations and experimental confirmation.