Discovery of potential epidermal growth factor receptor inhibitors from black pepper for the treatment of lung cancer: an in-silico approach.

Autor: Elekofehinti OO; Bioinformatics and Molecular Biology Unit, Department of Biochemistry, Federal University of Technology Akure, Akure, Ondo State Nigeria.; Teady Bioscience Research Laboratory, C28, Plural Gardens Estate, Akure, Ondo State Nigeria., Adetoyi IR; Bioinformatics and Molecular Biology Unit, Department of Biochemistry, Federal University of Technology Akure, Akure, Ondo State Nigeria.; Teady Bioscience Research Laboratory, C28, Plural Gardens Estate, Akure, Ondo State Nigeria., Popoola HO; Phytomedicine Biochemical Pharmacology and Toxicology Unit, Department of Biochemistry, Federal University of Technology Akure, Akure, Ondo State Nigeria., Ayodeji FO; Bioinformatics and Molecular Biology Unit, Department of Biochemistry, Federal University of Technology Akure, Akure, Ondo State Nigeria.; Teady Bioscience Research Laboratory, C28, Plural Gardens Estate, Akure, Ondo State Nigeria., Taiwo FA; Bioinformatics and Molecular Biology Unit, Department of Biochemistry, Federal University of Technology Akure, Akure, Ondo State Nigeria.; Teady Bioscience Research Laboratory, C28, Plural Gardens Estate, Akure, Ondo State Nigeria., Akinjiyan MO; Bioinformatics and Molecular Biology Unit, Department of Biochemistry, Federal University of Technology Akure, Akure, Ondo State Nigeria.; Teady Bioscience Research Laboratory, C28, Plural Gardens Estate, Akure, Ondo State Nigeria., Koledoye OF; Phytomedicine Biochemical Pharmacology and Toxicology Unit, Department of Biochemistry, Federal University of Technology Akure, Akure, Ondo State Nigeria., Iwaloye O; Bioinformatics and Molecular Biology Unit, Department of Biochemistry, Federal University of Technology Akure, Akure, Ondo State Nigeria.; Teady Bioscience Research Laboratory, C28, Plural Gardens Estate, Akure, Ondo State Nigeria., Adegboyega AE; Department of Biochemistry, Faculty of Basic Medical Sciences, University of Jos, Jos, Plateau State Nigeria.; Bioinformatics Unit, Jaris Computational Biology Centre, Jos, Plateau State Nigeria.
Jazyk: angličtina
Zdroj: In silico pharmacology [In Silico Pharmacol] 2024 Apr 08; Vol. 12 (1), pp. 28. Date of Electronic Publication: 2024 Apr 08 (Print Publication: 2024).
DOI: 10.1007/s40203-024-00197-1
Abstrakt: A tyrosine kinase receptor known as epidermal growth factor receptor (EGFR) is one of the main tumour markers in many cancer types and also plays a crucial role in cell proliferation, differentiation, angiogenesis, and apoptosis, which is a result of the auto-phosphorylations (kinase activity enhancement) that trigger signals involved in different cellular processes. Due to the discovery that non-small cell lung cancer (NSCLC) is a cause of this kinase activity enhancement, so far, several inhibitors have been tested against EGFR, but the side effects of these inhibitors necessitate an urgent measure to come up with an inhibitor that will be more specific to the cancer cells and not affect self-cells. This study was conducted to evaluate the efficacy of 37 compounds derived from Piper nigrum against EGFR using computer-aided drug design. Based on molecular docking, induced-fit docking, calculation of free binding energy, pharmacokinetics, QSAR prediction, and MD simulation. We propose five (5) lead compounds (clarkinol A, isodihydrofutoquinol B, Burchellin, kadsurin B, and lancifolin C) as a novel inhibitor, with clarkinol A demonstrating the highest binding affinity (-7.304 kcal/mol) with EGFR when compared with the standard drug (erlotinib). They also showed significant moderation for parameters investigated for a good pharmacokinetic profile, with a reliable R2 coefficient value predicted using QSAR models. The MD simulation of clarkinol A was found to be stable within the EGFR binding pocket throughout the 75 ns simulation run time. The findings showed that clarkinol A derived from Piper nigrum is worth further investigation and consideration as a possible EGFR inhibitor for the treatment of lung cancer.
Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-024-00197-1.
Competing Interests: Conflict of interestThe authors declares that they have no conflict of interest
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Databáze: MEDLINE
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