Inhibitory Potential of the Ocimum sanctum Phytochemicals on Bruton's Tyrosine Kinase, a Well-Known Drug Target for Treatment of Chronic Lymphocytic Leukemia: An In Silico Investigation

Shabir Ahmad Mir; Yahya Madkhali; Ahmad Firoz; Ayoub Al Othaim; Wael Alturaiki; Sami G Almalki; Abdulrahman Algarni; Suliman A Alsagaby

doi:10.3390/molecules28083287

Inhibitory Potential of the Ocimum sanctum Phytochemicals on Bruton's Tyrosine Kinase, a Well-Known Drug Target for Treatment of Chronic Lymphocytic Leukemia: An In Silico Investigation

Molecules. 2023 Apr 7;28(8):3287. doi: 10.3390/molecules28083287.

Authors

Shabir Ahmad Mir^{1

2}, Yahya Madkhali¹, Ahmad Firoz³, Ayoub Al Othaim¹, Wael Alturaiki¹, Sami G Almalki¹, Abdulrahman Algarni⁴, Suliman A Alsagaby¹

Affiliations

¹ Department of Medical Laboratory Sciences, College of Applied Medical Science, Majmaah University, Al Majmaah 11952, Saudi Arabia.
² Health and Basic Sciences Research Center, Majmaah University, Al Majmaah 11952, Saudi Arabia.
³ Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
⁴ Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Northern Border University, Arar 91431, Saudi Arabia.

Abstract

Chronic lymphocytic leukemia (CLL) is an incurable neoplasm of B-lymphocytes, which accounts for about one-third of all leukemias. Ocimum sanctum, an herbaceous perennial, is considered as one of the important sources of drugs for the treatment of various diseases, including cancers and autoimmune diseases. The present study was designed to screen various phytochemicals of O. sanctum for discovering their potential to inhibit Bruton's tyrosine kinase (BTK), a well-known drug target of CLL. Various phytochemicals of O. sanctum were screened for their potential to inhibit BTK using several in silico protocols. First, the molecular docking approach was used to calculate the docking scores of the selected phytochemicals. Then, the selected top-ranked phytochemicals were screened for their physicochemical characteristics using ADME analysis. Finally, the stability of the selected compounds in their corresponding docking complexes with BTK was analysed using molecular dynamics simulations. Primarily, our observations revealed that, out of the 46 phytochemicals of O. sanctum, six compounds possessed significantly better docking scores (ranging from -9.2 kcal/mol to -10 kcal/mol). Their docking scores were comparable to those of the control inhibitors, acalabrutinib (-10.3 kcal/mol), and ibrutinib (-11.3 kcal/mol). However, after ADME analysis of these top-ranked six compounds, only three compounds (Molludistin, Rosmarinic acid, and Vitexin) possessed drug likeliness characteristics. During the MD analysis, the three compounds Molludistin, Rosmarinic acid, and Vitexin were found to remain stable in the binding pocket in their corresponding docking complexes with BTK. Therefore, among the 46 phytochemicals of O. sanctum tested in this study, the three compounds, Molludistin, Rosmarinic acid, and Vitexin are the best inhibitors of BTK. However, these findings need to be confirmed by biological experiments in the laboratory.

Keywords: Ocimum sanctum; cancer; chronic lymphocytic leukemia; in silico; molecular docking; phytochemicals.

MeSH terms

Agammaglobulinaemia Tyrosine Kinase / metabolism
Humans
Leukemia, Lymphocytic, Chronic, B-Cell* / drug therapy
Leukemia, Lymphocytic, Chronic, B-Cell* / metabolism
Molecular Docking Simulation
Ocimum sanctum / metabolism
Protein Kinase Inhibitors / chemistry
Rosmarinic Acid

Substances

Agammaglobulinaemia Tyrosine Kinase
Protein Kinase Inhibitors

Grants and funding

This study was financially supported by the Deanship of Scientific Research at Majmaah University, Al Majma’ah, Saudi Arabia (Project number: R-2023-286).