Objective: The present investigation aims to predict the pharmacokinetic aspects and assessing the anti-Alzheimer’s activity using both molecular docking platform and ex vivo pharmacological studies on muscle contraction. Materials and Methods: 2-Methyl Anthraquinone (MAQ) and Quinizarine (QNZ) were isolated from Rubia cordifolia L., and evaluated for absorption, distribution, metabolism, excretion, and toxicity. Molecular docking was performed with the help of Mcule software on five drug targets acetylcholinesterase enzyme (AChE), cyclin-dependent kinase5 (CDK5), glycogen synthase kinase 3β (GSK3β), monoamine oxidase (MAO-B), and β-secretase enzyme (BACE). The pharmacological activity was screened by recording the muscle contractions of chick ileum. Results: The selected compounds were following Lipinski rule of five and the in silico studies have shown that the compounds possess drug likeliness, appreciated absorption, distribution, admired bioavailability, acceptable toxicity profile, and ability to cross the blood-brain barrier. The multi-target screening of AChE, CDK5, MAOB, GSK3β, and BACE for MAQ and QNZ showed greater binding energy of −9.9, −10, −10.5, −9.4, and 8.2 kcal/mol and −9.6, −9.1, −9.9, −8.9, and 7.8 kcal/mol, respectively. The ex vivo studies have shown to possess synergistic effect in increasing the muscle contractility response of MAQ and QNZ with acetylcholine. Conclusion: The in silico parameters have shown good pharmacokinetic profile of the isolated compounds. The binding energy and affinity of amino acids with ligands have similar behavior in the ex vivo studies. It is suggested that the isolated compounds have promising anti-Alzheimer’s activity. Further studies are required to confirm the possibility of anti-Alzheimer’s activity of the selected compounds.
Faculty of Pharmaceutical Sciences, Chulalongkorn University
Srinivasulu, Pottella; Babu, Janga Ramesh; Kumar, T.N.V. Ganesh; Kumar, Padarthi Pavan; and Vidyadhara, S.
"Anthraquinones extracted from
Rubia cordifolia Linn as potential ligands to treat Alzheimer’s disease,"
The Thai Journal of Pharmaceutical Sciences: Vol. 45:
3, Article 3.
Available at: https://digital.car.chula.ac.th/tjps/vol45/iss3/3