β-SECRETASE INHIBITORY ACTIVITY OF CLERODANE DITERPENOIDS AND APORPHINOID ALKALOIDS AND INSIGHT FROM IN SILICO ANALYSES

The β-secretase, which is a β-site amyloid precursor protein cleaving enzyme 1 (BACE1), starts the synthesis of toxic amyloid β (Aβ), which is a key early factor in the pathophysiology of Alzheimer’s disease (AD). No cure for AD so far which necessitate the search for new neurotherapeutic agents especially from natural products (NPs). Inhibiting BACE1 using NP’s inhibitors is considered a promising strategy. The study aims to evaluate the BACE 1 inhibitory potentials of clerodane diterpenoids and aporphinoid alkaloids from the stem of Tinospora cordifolia (Willd.) Miers ex Hook. F. & Thoms (Menispermaceae) and get Insight from in silico analyses using molecular docking and MM-GBSA. The enzyme assay was done in vitro using the UV-spectroscopic method. Molecular docking was carried out using Maestro software (Schrödinger). Ligands were docking with PDB ID: 3DV1 complex with NVP-ARV999. 8-hydroxycolumbin, a clerodane diterpenoid have the highest potential to inhibit the enzyme β-secretase (IC50 = 0.040±0.00 mg/mL, 58.58% inhibition) when compared to quercetin (IC50 = 0.055±0.00 mg/mL, 72.32% inhibition) at 0.1 mg/mL. Molecular docking demonstrated the presence of hydrogen bonding and π-π Interactions between ligands and enzyme active sites. N-formylanonaine has the best (ΔGbind) (MM-GBSA) (-28.64 kcal/mol) followed by corydine (-21.64 kcal/mol). N-formylanonaine, corydine and 8-hydroxycolumbin could be a template in the discovery of new neurotherapeutic agent in the management of AD due to their abilities to effectively bind to β-secretase protein residues