Pharmacological Properties of Linearolactone against the Amoebiasis Caused by Entamoeba histolytica: An In Silico Study

Linearolactone (LL) isolated from Salvia polystachya presents antiparasitic activity against E. histolytica and G. lamblia through ROS production, an apoptosis-like process, alteration of the actin cytoskeleton. This effect limits invasion spread parasites during host infection. However, possible toxicological effects or molecular mechanisms by which LL affects mobility are still not understood. could act as inhibitor accessory cytoskeletal proteins, such myosin, calreticulin, calpain to achieve this end. The aim study was determine pharmacological properties via bioinformatic analyses find therapeutic targets understand action mechanism on cytoskeleton histolytica. activities, risks, were determined using free software Molsoft© define bioactivity comparison with standard drugs [1], Molinspiration© calculate physicochemical [2], ToxiM© intestinal permeability [3,4], SuperCYPsPred© predict drug metabolism cytochrome-P450 system [5,6], SEA© proteins binding sites for active compounds inverse protein–ligand approach [7,8]. Molecular docking key pathogenic trophozoites, myosin-II performed AutoDock-Vina UCSF-Chimera. Results revealed that a drug-likeness −0.55 ToxiM 0.958 due medium toxicity associated interactions in nuclear receptors (0.66), GPCR ligands (0.65), enzymatic inhibitions (0.47) related (CYP3A4, low). indicate is hydrophobic molecule (LogP: 1.59) intermediate absorption (TPSA: 65.75, CACO-2 permeability) blood–brain barrier penetration (3.86). SEA analysis demonstrated potential target pharmacophores OPRK1 (p-Value: 6.49 × 10−37, Max TC: 0.49) NLRP3 3.90 10−19, 0.36) humans. showed high affinity ATP-binding catalytic heavy-chain (GLU-187.A, THR-186.A, ASN-234.B) (−8.30 Kcal/mol), well chain A C (LYS-199.A, LYS-152.C) calreticulin (−8.77 Kcal/mol). As conclusions, compound moderate toxicity, sedative CNS, anti-inflammatory properties. In addition, has involving immobilization trophozoites calreticulin. These present parasite fundamental amoebic liver abscess formation Therefore, be alternative amoebiasis treatment provide leading discovery parasitic diseases, but in-depth studies necessary confirm these claims.