Exploring Scutellaria baicalensis bioactives as EGFR tyrosine kinase inhibitors: Cheminformatics and molecular docking studies

• Published in: Informatics in medicine unlocked Vol. 43; p. 101406
• Main Authors: Yusuf, Amina J., Adegboyega, Abayomi E., Yakubu, Abdulbasit H., Johnson, Grace I., Asomadu, Rita O., Adeduro, Mary N., Chukwuma, Ifeoma F., Ugwah-Oguejiofor, Chinenye J., Okoh, Olayinka S., Johnson, Titilayo O.
• Format: Journal Article
• Language: English
• Published: Elsevier 2023
• Subjects: Bioactive compounds; Cancer therapy; Computational drug discovery; EGFR tyrosine kinase; Natural products; Scutellaria baicalensis
• ISSN: 2352-9148; 2352-9148
• DOI: 10.1016/j.imu.2023.101406

The Epidermal Growth Factor Receptor (EGFR) pathway plays a pivotal role in cancer progression, making it a prime target for anticancer drug development. Scutellaria baicalensis, a traditional Chinese medicinal herb, harbors bioactive compounds with promising pharmacological properties, including potential EGFR tyrosine kinase inhibition. In this study, we employed a comprehensive approach merging cheminformatics and molecular docking techniques to investigate the glioblastoma multiforme inhibitory potentials of the bioactive compounds from the plant, with a focus against EGFR. Our findings revealed significant binding affinities ranging from −9.010 to −6.427 kcal/mol and intricate molecular interactions between compounds from S. baicalensis and the EGFR. Notably, Ganhuangenin, 5,7,2′,5′-tetrahydroxyflavone, (2R)-2-(2,6-dihydroxyphenyl)-3,4-dihydro-2H-chromene-5,7-diol, and tenaxin I showed particularly high binding affinities, with scores ranging from −9.010 to −8.649 kcal/mol. These compounds even outperformed erlotinib, a standard ligand with a score of −8.539 kcal/mol. Importantly, they interacted with key amino acid residues (Met769, Glu738, and Thr766) through hydrogen bonding. These interactions were driven by specific structural features, including aromatic rings, hydrogen bond donors and acceptors, and hydrophobic interactions and the reliability of these results was further confirmed through induced-fit docking, reinforcing the potential inhibitory effects of these compounds on the flexible protein. Additionally, all of the top-scoring compounds from S. baicalensis adhered to established drug-likeness rules, including Lipinski's criteria, Ghose's rules, Veber's guidelines, and Egan's rules. However, it's worth noting that scutellarin had some violations in these rules. Remarkably, none of the identified compounds were likely to cause hepatotoxicity, mutagenicity, or cytotoxicity, suggesting that they could be considered as safe candidates for anti-cancer agents. This multidisciplinary investigation bridges traditional herbal knowledge and modern drug discovery, offering insights into the potential of S. baicalensis bioactive compounds as novel EGFR-targeting agents. The results underscore the value of chemoinformatics and molecular docking studies in exploring natural compounds for cancer therapy, paving the way for further research in the field.