The in vitro and in silico Anticholinesterase Ac-tivities of Brittle Star (Ophiocoma erinaceus) crude venoms from the Persian Gulf-Bushehr

Background: Brittle stars can produce well-known toxins responsible for various of their biological activities in addition to their physical defense. The purpose of this study was to identify secondary metabolites and assess the anticholinesterase activities of the crude venom of the Persian Gulf Ophiocoma erinaceous (brittle star) in vitro and in silico due to the abundance of this marine life on the Persian Gulf coasts and with knowledge of their numerous biological effects. Materials and Methods: In this study, after the lyophilization of the brittle star sample, an LD50 test, a test of cholinesterase inhibitory activities, identification of the secondary metabolites, and their in-silico evaluations were performed by, respectively, Spearman-Karber, the Ellman spectroscopic method, Gas Chromatography–Mass Spectrometry (GC-MS), and computational docking method. Results: According to the results, the LD50 value of the sample was 6.04±0.13 (mg/kg). The IC50 values related to their Acetylcholinesterase and  Butyrylcholinesterase were 37.925 ±0.055 and 5.388±0.02 (μg/ml), respectively, compared to the galantamine standard. The GC-MS analysis of the sample showed 25 bioactive chemical compositions with different structures, such as alkaloids, terpenes, and steroids. The computational results of the compounds also confirmed the experimental results. Among these, the alkaloidal compound BS4, had the highest affinity for both enzymes. Conclusion: As for toxicity potency, the brittle star crude venom sample was classified in the highly toxic category. The GC analysis of the crude venom showed various bioactive secondary metabolites with different chemical structures. The experimental and computational results on the anticholinesterase activities of the sample showed that the venom acts as a significant inhibitor of both enzymes. Further studies are required to determine whether the compound BS4 could be a candidate for the treatment of Alzheimer’s disease.