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© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

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.

Details

Title
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
Author
Shabir Ahmad Mir 1   VIAFID ORCID Logo  ; Madkhali, Yahya 2 ; Ahmad, Firoz 3   VIAFID ORCID Logo  ; Ayoub Al Othaim 2 ; Alturaiki, Wael 2   VIAFID ORCID Logo  ; Almalki, Sami G 2   VIAFID ORCID Logo  ; Algarni, Abdulrahman 4 ; Alsagaby, Suliman A 2   VIAFID ORCID Logo 

 Department of Medical Laboratory Sciences, College of Applied Medical Science, Majmaah University, Al Majmaah 11952, Saudi Arabia; Health and Basic Sciences Research Center, Majmaah University, Al Majmaah 11952, Saudi Arabia 
 Department of Medical Laboratory Sciences, College of Applied Medical Science, Majmaah University, Al Majmaah 11952, Saudi Arabia 
 Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia 
 Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Northern Border University, Arar 91431, Saudi Arabia 
First page
3287
Publication year
2023
Publication date
2023
Publisher
MDPI AG
e-ISSN
14203049
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2806593080
Copyright
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.