Targeting small druggable compounds against 3RZE histamine H1 receptor as potential of anti-allergic drug applying molecular modeling approach

Abstract

Abstract Background Allergic disorders, prevalent global health concerns, afflict a substantial portion of the world’s population. These maladies result from an exaggerated immune system response to ordinarily innocuous substances, such as pollen, dust mites, and specific dietary components. Clinical manifestations of this heightened immune response include itching, swelling, and respiratory impairment, often accompanied by releasing mediators like histamine. The pathophysiological mechanisms of allergy disorders are intricate, arising from a complex interplay between genetic and environmental factors. While clinical presentations may vary, all allergy conditions share a common foundation in the dysregulated immune response to allergens. Result The current aim of this study was to identify innovative anti-allergic agents capable of inhibiting histamine and effectively mitigating allergic reactions by utilizing the computer-aided drug design approach by discovery studio (DS) 2022 v 23.1.1 package. The overarching aim was identifying potential drug candidates targeting the active site within the histamine H1 receptor complex; therefore, a collection of 4000 small druggable compounds was curated from ZINC, PubChem, and DRUG BANK databases sources. Four compounds appeared as promising candidates after assessing docking scores and binding energies. Notably, Compound ID 34154, recognized as tymazoline, showed the highest affinity for the H1 receptor of 3RZE, suggesting it may be the most promising choice for more research. Further chemoinformatic and ADMET (absorption, distribution, metabolism, excretion, and toxicity) analyses were conducted to assess the drug-like qualities of this chosen molecule. In addition, bioisosteric substitution techniques were employed to enhance tymazoline’s ADMET characteristics. Conclusion Tymazoline shows strong binding affinity with 3RZE and verified all the drug-likeness criteria to inhibit the allergic disorders. Furthermore, molecular dynamics (MD) studies corroborated tymazoline’s potential as an anti-allergic agent, demonstrating contact between the ligand and the receptor that is well defined and stable.

Keywords

• MD simulation
• Molecular docking
• Anti-allergic
• Tymazoline
• Small druggable compound