Phytochemical and in silico study on Lupinus subcarnosus Hook, its effect on neuronal α4β2 nicotinic acetylcholine receptors (nAChRs) and the major alkaloids

Mohamed, Mahmoud; Aly, Omar M.; Alghamdi, Saleh Abdullah; Alquraini, Ali; Alzahrani, Abdulaziz; Alghamdi, Adel; M. Shatla, Ibrahim; El Shorbagi, Abd El Nasser; Chaudhary, Sachin; Mustafa, Muhamad

doi:10.21608/odr.2022.155742.1007

Phytochemical and in silico study on Lupinus subcarnosus Hook, its effect on neuronal α4β2 nicotinic acetylcholine receptors (nAChRs) and the major alkaloids

Document Type : Research Articles

Authors

¹ Pharmacognosy Department, College of Clinical Pharmacy, Albaha University, Saudi Arabia

² Department of Medicinal Chemistry, Faculty of Pharmacy, Port Said University

³ Clinical pharmacy department, College of Clinical Pharmacy,‬ ‪ ‬ ‪AlBaha University, Saudi Arabia‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬

⁴ Pharmaceutical chemistry department, College of Clinical Pharmacy,‬ ‪AlBaha University, Saudi Arabia‬‬‬‬‬‬‬‬‬‬

⁵ Pharmaceutical chemistry department, College of Clinical Pharmacy,‬ ‪ ‬ ‪AlBaha University, Saudi Arabia

⁶ Department of Physiology, Damietta Faculty of Medicine, Al-Azhar University, Egypt

⁷ Department of Medicinal Chemistry, Faculty of Pharmacy, Al Sharjah University, United Arab Emirates.

⁸ IBMM, Univ. Montpellier, ENSCM, Montpellier, France

10.21608/odr.2022.155742.1007

Abstract

Neuronal nicotinic acetylcholine receptors, including α4 and β2 subunits, are the amplest nicotinic acetylcholine receptors present in the brain. Nicotine is a component of tobacco smoke that exerts its psychoactive impacts via binding to nicotinic acetylcholine receptors (nAChRs). Thus, targeting α4β2 of the nAChRs is emerging as a promising tool implemented for smoking cessation. We isolated twelve (1-12) alkaloids from 75% EtOH extract of L. subcarnosus herb for the first time. The structures of the isolated alkaloids were established by spectroscopic methods, by comparison with authentic samples. Based on the structural similarities between the approved smoking cessation drugs cytisine and varenicline, the isolated alkaloids (1-12) were docked into the α4β2 nAChR active site. Compounds 9 and 11 revealed reasonable binding energy and interacted with the key amino acids Cys199, Cys200, and Trp156 within α4β2 nAChR active site. The in silico ADME prediction toxicity and mutagenicity of lupin alkaloids were studied as well.

Keywords