Identification of Some Promising Heterocycles Useful in Treatment of Allergic Rhinitis: Virtual Screening, Pharmacophore Mapping, Molecular Docking, and Molecular Dynamics

Xiaopeng Sun; Amany Belal; Mohamed A Elanany; Reem I Alsantali; Munira M Alrooqi; Abdalla R Mohamed; Sherifa Hasabelnaby

doi:10.1134/S1068162022330019

Identification of Some Promising Heterocycles Useful in Treatment of Allergic Rhinitis: Virtual Screening, Pharmacophore Mapping, Molecular Docking, and Molecular Dynamics

Russ J Bioorg Chem. 2022;48(2):438-456. doi: 10.1134/S1068162022330019. Epub 2022 May 26.

Authors

Xiaopeng Sun¹, Amany Belal², Mohamed A Elanany³, Reem I Alsantali², Munira M Alrooqi⁴, Abdalla R Mohamed⁵, Sherifa Hasabelnaby⁶

Affiliations

¹ Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital of Xi'an Medical University, 710038 Xi'an, Shaanxi China.
² Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, P.O. Box 11099 Taif, 21944 Saudi Arabia.
³ School of Pharmacy and Pharmaceutical Industries, Badr University in Cairo (BUC), Cairo, Egypt.
⁴ Department of Chemistry, Faculty of Applied Science, Umm Al-Qura University, 21955 Makkah, Saudi Arabia.
⁵ Pharmaceutical Chemistry Department, Faculty of Pharmacy, Egyptian Russian University, 11829 Cairo Badr City, Egypt.
⁶ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Helwan, Egypt.

Abstract

Rhinitis is an allergic disease that causes troubles and restlessness for patients. In this research work we will focus on finding promising organic molecules with potential ability to target histamine receptor with no sedative side effect. Phalazines and their isosteres, pyrimidines and pyridines have been reported to target H1 receptors, for this reason we have searched for library of these basic scaffolds, this library which has 184 organic molecules will be subjected for further explorations through computer aided drug design techniques. Swiss ADMET will be used to gather these compounds in clusters. Cluster with low potential to penetrate BBB is selected for virtual screening through pharmacophore model. Then molecular docking that revealed the stability of the complex formed between the investigated molecules and H1 receptor. ADMET profile showed three compounds (XVIII), (XX), and (XXI) with no toxicity on liver and no effect on CYP2D6, these three compounds were subjected to molecular dynamic simulations and compound (XVIII) showed the most stable complex with the target protein (H1). Finally, we can say this work helped us to find new compounds with promising potential to target H1 without ability to penetrate BBB, so they can be used as useful candidates in treatment of rhinitis and deserve to be subjected for preclinical and clinical investigations.

Supplementary information: The online version contains supplementary material available at 10.1134/S1068162022330019.

Keywords: histamine H1; molecular docking; molecular dynamics; pharmacophores; phthalazine; pyridines; pyrimidines; rhinitis; virtual screening.