Structure-Based Profiling of Potential Phytomolecules with AKT1 a Key Cancer Drug Target
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Published:2023-03-13
Issue:6
Volume:28
Page:2597
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ISSN:1420-3049
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Container-title:Molecules
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language:en
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Short-container-title:Molecules
Author:
Mirza Zeenat12, Karim Sajjad23ORCID
Affiliation:
1. King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia 2. Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia 3. Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Abstract
Identifying cancer biomarkers is imperative, as upregulated genes offer a better microenvironment for the tumor; hence, targeted inhibition is preferred. The theme of our study is to predict molecular interactions between cancer biomarker proteins and selected natural compounds. We identified an overexpressed potential molecular target (AKT1) and computationally evaluated its inhibition by four dietary ligands (isoliquiritigenin, shogaol, tehranolide, and theophylline). The three-dimensional structures of protein and phytochemicals were retrieved from the RCSB PDB database (4EKL) and NCBI’s PubChem, respectively. Rational structure-based docking studies were performed using AutoDock. Results were analyzed based primarily on the estimated free binding energy (kcal/mol), hydrogen bonds, and inhibition constant, Ki, to identify the most effective anti-cancer phytomolecule. Toxicity and drug-likeliness prediction were performed using OSIRIS and SwissADME. Amongst the four phytocompounds, tehranolide has better potential to suppress the expression of AKT1 and could be used for anti-cancer drug development, as inhibition of AKT1 is directly associated with the inhibition of growth, progression, and metastasis of the tumor. Docking analyses reveal that tehranolide has the most efficiency in inhibiting AKT1 and has the potential to be used for the therapeutic management of cancer. Natural compounds targeting cancer biomarkers offer less rejection, minimal toxicity, and fewer side effects.
Funder
Institutional Fund Projects Ministry of Education and King Abdulaziz University, DSR, Jeddah, Saudi Arabia
Subject
Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science
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