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.

Keywords:

• Sida rhombifolia
• Alzheimer’s disease
• molecular docking
• DFT
• ADMET
• RC plot

Acknowledgement

The authors acknowledge Dr. S. Athimoolam, Department of Physics, University College of Engineering, Anna University, Nagercoil for helping us in utilizing Gaussian 09 Program.

Author contributions

The work was carried out in collaboration among all authors. Conceptualization was by A.Z. Graph theory network was performed by M.P. The retrieval of bioactive phytochemicals and active site prediction was performed by M.P., A.Z. and K.C. The Molecular docking was done by M.P. and K.A. Pharmacokinetic parameters was predicted by M.P. and A.Z. Density function Theory was performed by M.P., A.Z. and A.B.S. The RC plot analysis was done by A.Z. and C.C. The draft of the manuscript was written by M.P. and A.Z. Validation of the manuscript was done by A.Z. and A.B.S. All authors read and approved the final manuscript.

Disclosure statement

The authors have no relevant financial or non-financial interests to disclose.

Additional information

Funding

The authors declare that no funds, grants, or other support were received during this study.