Graph Theory Network, Molecular Docking, Quantum Chemicals and Pharmacokinetics-Based Investigation on Phytochemicals from Sida rhombifolia against Alzheimer’s Disease

Abstract

Sida rhombifolia also referred as “Bala” plant was found throughout the tropics and nurtures in warm climates and possesses various pharmacological properties like anti-diabetic, anti-inflammatory, antifungal, anti-arthritic, antibacterial and anti-diarrheal. We examine about eighteen bioactive phytochemicals from S.rhombifolia against Alzheimer’s disease. The target proteins BACE1 and Aβ were selected based on graph theory network analysis. These eighteen bioactive compounds along with a known standard were docked against target proteins and their binding affinity falls between the range −3.7 Kcal/mol to −8.6 Kcal/mol. The top hit was observed for cryptolepine with a score of −8.3 Kcal/mol (BACE1) and −8.6 Kcal/mol (Aβ) followed by riboflavin with −8.1 Kcal/mol (BACE1) and 8.4 (Aβ). These two top-hit compounds were further investigated through frontier molecular orbitals to analyze the structural stability and reactivity using DFT/B3LYP–LanL2DZ basis set. The observed energy gap showed that cryptolepine (2.55786 eV) and riboflavin (3.3625 eV) exhibit better reactivity and its electrostatic potential map showed charge distribution over the atoms. The pharmacokinetic studies and toxicity analysis showed the drug-likeness and safety profile of cryptolepine and riboflavin. Further, the Ramachandran plot confirms the stability of the amino residues interacting with ligands. This study will support the use of Sida rhombifolia in conventional treatment and the beginning of the development of a novel drug against alzheimer’s disease through in vitro model.